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Trial record 1 of 4 for:    19726763 [PUBMED-IDS]
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GDC-0449 in Treating Patients With Locally Advanced or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT00607724
Recruitment Status : Completed
First Posted : February 6, 2008
Results First Posted : October 8, 2015
Last Update Posted : October 8, 2015
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Unspecified Adult Solid Tumor, Protocol Specific
Intervention Drug: GDC-0449
Enrollment 68
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] Stage 2: New Formulation [GDC-0449 (150 mg )]
Hide Arm/Group Description Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 milligram (mg) on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST v1.0), maximum benefit, or intolerability. Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability. Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability. Participants with basal cell carcinoma (BCC) received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Period Title: Stage 1: Dose Escalation
Started 7 9 4 0 0 0 0
Completed 0 1 [1] 0 0 0 0 0
Not Completed 7 8 4 0 0 0 0
Reason Not Completed
Tumour Progression−Clinical/Radiographic             7             8             4             0             0             0             0
[1]
Participants still on treatment at time of study closure were considered ‘completers’.
Period Title: Stage 2: Expanded Cohort
Started 0 0 0 6 14 12 16
Completed 0 0 0 1 [1] 5 [1] 0 5 [1]
Not Completed 0 0 0 5 9 12 11
Reason Not Completed
Adverse Event             0             0             0             0             0             0             1
Tumour Progression−Clinical/Radiographic             0             0             0             4             8             11             10
Physician Decision             0             0             0             0             1             1             0
Withdrawal by Subject             0             0             0             1             0             0             0
[1]
Participants still on treatment at time of study closure were considered ‘completers’.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] Stage 2: New Formulation [GDC-0449 (150 mg )] Total
Hide Arm/Group Description Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability. Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability. Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability. Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability. Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability Total of all reporting groups
Overall Number of Baseline Participants 7 9 4 6 14 12 16 68
Hide Baseline Analysis Population Description
Safety-evaluable population included all participants who received any amount of GDC-0449.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 9 participants 4 participants 6 participants 14 participants 12 participants 16 participants 68 participants
57.6  (10.5) 59.9  (12.6) 42.3  (15.3) 54.2  (15.3) 54.7  (11.2) 55.3  (14.8) 54.6  (11.0) 55.0  (12.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 9 participants 4 participants 6 participants 14 participants 12 participants 16 participants 68 participants
Female
2
  28.6%
5
  55.6%
1
  25.0%
1
  16.7%
4
  28.6%
5
  41.7%
6
  37.5%
24
  35.3%
Male
5
  71.4%
4
  44.4%
3
  75.0%
5
  83.3%
10
  71.4%
7
  58.3%
10
  62.5%
44
  64.7%
1.Primary Outcome
Title Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Hide Description A DLT was defined as any Grade 3 or 4 hematologic or major organ toxicity as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) that occurred during the first 35 days after the initiation of study drug (Days 1−35) and was attributable to GDC-0449.
Time Frame Up to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety-evaluable population.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma (GDC-0449 [150 mg]) Stage 2: Basal Cell Carcinoma (GDC-0449 [270 mg]) Stage 2:Safety Expansion Cohort (GDC-0449 [150 mg]) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received GDC-0449 Phase II drug product as 150-mg hard gelatin capsules daily, orally, starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 7 9 4 6 14 12 16
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0 0 0 0
2.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) After a Single Dose of GDC-0449
Hide Description Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and pharmacodynamic (PD) data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial.
Time Frame -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and – 5 minutes (pre-dose) on Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-evaluable population included participants who had at least Day 1 PK samples available.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 7 9 4 16
Mean (Standard Deviation)
Unit of Measure: micromolar (mcM)
Phase I 3.58  (1.34) 6.34  (3.40) 6.81  (2.69) NA [1]   (NA)
Phase II NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 7.2  (3.38)
[1]
The arm was only valid for Phase II.
[2]
The arm was only valid for Phase I.
3.Primary Outcome
Title Cmax After Multiple Doses of GDC-0449
Hide Description Cmax was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve.
Time Frame -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Cmax was not reported as there were <50% participants with extensive PK sampling and the PK profiles were flat over 24 hours at steady state which did not allow estimation of Cmax.
Arm/Group Title Stage 1+Stage 2: GDC-0449 (150 mg) Stage 1+Stage 2: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg)
Hide Arm/Group Description:
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 150 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 270 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Primary Outcome
Title Time to Maximum Plasma Concentration (Tmax) After a Single Dose of GDC-0449
Hide Description Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and PD data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial.
Time Frame -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and – 5 minutes (pre-dose) on Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable population.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 7 9 4 16
Median (Full Range)
Unit of Measure: days
Phase I
2
(0.0417 to 7)
2
(1 to 3)
2.5
(0.167 to 3)
NA [1] 
(NA to NA)
Phase II
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
NA [2] 
(NA to NA)
1
(0.0833 to 1)
[1]
The arm was only valid for Phase II.
[2]
The arm was only valid for Phase I.
5.Primary Outcome
Title Tmax After Multiple Doses of GDC-0449
Hide Description Tmax was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve.
Time Frame -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Cmax was not reported as there were <50% participants with extensive PK sampling and the PK profiles were flat over 24 hours at steady state which did not allow estimation of Cmax, and as Tmax was related to Cmax, it was also not estimated.
Arm/Group Title Stage 1+Stage 2: GDC-0449 (150 mg) Stage 1+Stage 2: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg)
Hide Arm/Group Description:
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 150 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 150 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Primary Outcome
Title Average Plasma Concentration at Steady State (Css, Avg) After Multiple Doses of GDC-0449
Hide Description Steady state GDC−0449 plasma concentrations (Css) were calculated as an average of plasma concentrations from Study Day 21 (Stage 2) or Study Day 28 (Stage 1) onward.
Time Frame -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable population. Here "number of participants analyzed" = participants evaluable for this measure.
Arm/Group Title Stage 1+Stage 2: GDC-0449 (150 mg) Stage 1+Stage 2: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 150 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 270 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 38 21 4 15
Mean (Standard Deviation)
Unit of Measure: mcM
23.1  (10.6) 19.8  (9.51) 22.2  (8.38) 24.5  (6.85)
7.Primary Outcome
Title Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) After a Single Dose of GDC-0449
Hide Description AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Phase I comprised of two stages, a dose-escalation stage with the goal of estimating the maximum tolerated dose (Stage 1), and an expanded cohort to collect additional safety, PK, and PD data at the proposed Phase II dose (Stage 2). Phase II represented the additional cohort initiated with 150 mg hard gelatin capsule identified from the safety, PK and PD data from Stage 1 of the trial.
Time Frame -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and – 5 minutes (pre-dose) on Day 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable population.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 7 9 4 16
Mean (Standard Deviation)
Unit of Measure: mcM*day
Phase I 2.22  (0.966) 4.24  (1.95) 4.79  (2.22) NA [1]   (NA)
Phase II NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 5.2  (2.79)
[1]
The arm was only valid for Phase II.
[2]
The arm was only valid for Phase I.
8.Primary Outcome
Title AUC0-24 After Multiple Doses of GDC-0449
Hide Description AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUC was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve.
Time Frame -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
AUC0-24 was not reported as there were <50% participants with extensive PK sampling and the PK profiles were flat over 24 hours at steady state which did not allow estimation of AUC0-24.
Arm/Group Title Stage 1+Stage 2: GDC-0449 (150 mg) Stage 1+Stage 2: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg)
Hide Arm/Group Description:
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 150 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 270 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Primary Outcome
Title Accumulation Index (AI) After Multiple Doses of GDC-0449
Hide Description AI was calculated using the formula [AI = AUC(0-24) on Day 15/AUC(0-24) on Day 1]. AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AI was estimated if there were extensive PK sampling in more that 50% of the participants to form a curve.
Time Frame -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
AI was not reported as there were <50% participants with extensive PK sampling and the PK profiles were flat over 24 hours at steady state which did not allow estimation of AI.
Arm/Group Title Stage 1: GDC-0449
Hide Arm/Group Description:
Included participants with any tumor who received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg, 270 mg and 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, 270 mg and 540 mg orally, continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Percentage of Participants With a Greater Than (>) 2-Fold Down-Modulation of GLI1 Expression in Skin Biopsy-Derived or Hair Follicle-Derived Messenger Ribonucleic Acid (mRNA)
Hide Description Ribonucleic acid (RNA) was extracted from biopsy specimens of noninvolved skin or hair follicles at baseline and at 7 and 21 days after the start of daily drug therapy. Control mRNA was obtained from formalin-fixed, paraffin-embedded samples of normal skin and hair follicles from participants who were not enrolled in the study.
Time Frame Baseline up to Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic-evaluable population included participants who had hair and/or skin samples available from Day 1 and at least one post-baseline sample while on study treatment. Here "number of participants analyzed" = participants evaluable for this measure and "n"= participants evaluable for the specific category.
Arm/Group Title All Participants
Hide Arm/Group Description:
Included all participants from Stage 1 and Stage 2.
Overall Number of Participants Analyzed 34
Measure Type: Number
Unit of Measure: percentage of participants
Skin biopsy (n = 34) 73.5
Hair follicle (n = 20) 30.0
11.Secondary Outcome
Title Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR): All Participants
Hide Description BOR was defined as the best objective response (complete or partial response determined by two consecutive investigator assessments which were at least 28 days apart) observed during the treatment period according to RECIST v1.0. CR: disappearance of all target lesions (TLs), with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 millimeters (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of TLs, taking as reference the baseline (BL) sum diameters.
Time Frame Screening, at Week 8 thereafter every 8 weeks, up to Week 116
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population were those with measurable disease at baseline and who received at least 1 dose of GDC-0449 and either had a post-baseline tumor assessment or progressed before any tumor assessment.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma (GDC-0449 [150 mg]) Stage 2: Basal Cell Carcinoma (GDC-0449 [270 mg]) Stage 2:Safety Expansion Cohort (GDC-0449 [150 mg]) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 7 9 4 6 14 10 16
Measure Type: Number
Unit of Measure: percentage of participants
14.3 11.1 0.0 66.7 42.9 0.0 37.5
12.Secondary Outcome
Title Percentage of Participants With a BOR of CR or PR: Participants With Basal Cell Carcinoma
Hide Description BOR was defined as the best objective response observed during the treatment period according to RECIST v1.0. CR: disappearance of all TLs, with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in the sum of diameters of TLs, taking as reference the BL sum diameters.
Time Frame Screening, at Week 8 thereafter every 8 weeks, up to Week 116
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population; only participants with BCC were included in the analysis.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma (GDC-0449 [150 mg]) Stage 2: Basal Cell Carcinoma (GDC-0449 [270 mg]) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 1 1 1 6 14 10
Measure Type: Number
Unit of Measure: percentage of participants
100.0 100.0 0.0 66.7 42.9 60.0
13.Secondary Outcome
Title Duration of Objective Response: All Participants
Hide Description Duration of response during first line therapy is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy.
Time Frame Screening, at Week 8 thereafter every 8 weeks, up to Week 116
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population; only participants who achieved a best overall response of CR or PR were included in the analysis.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma (GDC-0449 [150 mg]) Stage 2: Basal Cell Carcinoma (GDC-0449 [270 mg]) Stage 2:Safety Expansion Cohort (GDC-0449 [150 mg]) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 1 1 0 4 6 0 6
Median (95% Confidence Interval)
Unit of Measure: months
9.2 [1] 
(NA to NA)
NA [2] 
(NA to NA)
6.1 [3] 
(3.71 to NA)
NA [2] 
(5.72 to NA)
8.3 [3] 
(3.71 to NA)
[1]
Upper and lower limits of 95% CI could not be estimated as n=1.
[2]
Median duration of response could not be estimated as median duration of response had not been reached at the time of analysis.
[3]
Upper limit of CI could not be estimated due to consequence regarding occurrence of events and their censoring.
14.Secondary Outcome
Title Duration of Objective Response: Participants With BCC
Hide Description Duration of response during first line therapy is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy.
Time Frame Screening, at Week 8 thereafter every 8 weeks, up to Week 116
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable participants; only participants with BCC who achieved a best overall response of CR or PR were included in the analysis.
Arm/Group Title Stage 1+Stage 2: GDC-0449 (150 mg) Stage 1+Stage 2: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg)
Hide Arm/Group Description:
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 150 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 270 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 11 7 0
Median (Full Range)
Unit of Measure: months
8.3 [1] 
(3.71 to NA)
NA [2] 
(5.72 to NA)
[1]
Upper limit of CI could not be estimated due to consequence regarding occurrence of events and their censoring.
[2]
Median duration of response could not be estimated as median duration of response had not been reached at the time of analysis.
15.Secondary Outcome
Title Progression-Free Survival (PFS): All Participants
Hide Description PFS was defined as the time from first dose of GDC-0449 to documented disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using RECIST v1.0) or death from any cause within 30 days of the last dose of GDC-0449, whichever occurred first.
Time Frame Screening, at Week 8 thereafter every 8 weeks, up to Week 116
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population. Number of participants censored for Stage 1 150 mg, 270 mg, and 540 mg were 1, 2, and 1 subjects, respectively and for Stage 2 BCC 150 mg, 270 mg, Stage 2 Safety Expansion Cohort 150 mg, and Stage 2 New Formulation 150 mg were 2, 6, 1, and 6 subjects, respectively.
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma (GDC-0449 [150 mg]) Stage 2: Basal Cell Carcinoma (GDC-0449 [270 mg]) Stage 2:Safety Expansion Cohort (GDC-0449 [150 mg]) Stage 2: New Formulation (GDC-0449 [150 mg])
Hide Arm/Group Description:
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 7 9 4 6 14 10 16
Median (95% Confidence Interval)
Unit of Measure: months
2.0
(0.99 to 14.85)
1.6
(0.85 to 5.88)
2.1
(1.25 to 3.02)
9.6 [1] 
(5.75 to NA)
12.7 [1] 
(6.70 to NA)
1.8
(0.76 to 2.10)
7.1 [1] 
(0.99 to NA)
[1]
Upper limit of CI could not be estimated due to consequence regarding occurrence of events and their censoring.
16.Secondary Outcome
Title PFS: Participants With BCC
Hide Description PFS was defined as the time from first dose of GDC-0449 to documented disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using RECIST v1.0) or death from any cause within 30 days of the last dose of GDC-0449, whichever occurred first.
Time Frame Screening, at Week 8 thereafter every 8 weeks, up to Week 116
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population; only participants with BCC were included in the analysis. Number of participants censored for Stage 1+Stage 2 150 mg, and Stage 1+Stage 2 270 mg were 8 and 7 subjects, respectively, and no subject censored from Stage 1 540 mg group.
Arm/Group Title Stage 1+Stage 2: GDC-0449 (150 mg) Stage 1+Stage 2: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg)
Hide Arm/Group Description:
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 150 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor or BCC or safety expansion cohort received single or daily oral dose of GDC-0449 hard gelatin capsules at 270 mg starting on Day 1 (Stage 1 and Stage 2) and/or Day 8 (Stage 1), until disease progression, maximum benefit, or intolerability.
Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Overall Number of Participants Analyzed 17 15 1
Median (95% Confidence Interval)
Unit of Measure: months
10.8 [1] 
(6.67 to NA)
12.7 [1] 
(6.70 to NA)
1.2 [2] 
(NA to NA)
[1]
Upper limit of CI could not be estimated due to consequence regarding occurrence of events and their censoring.
[2]
Upper and lower limits of 95% CI could not be estimated as n=1.
Time Frame From Screening up to 28 days after the last dose of GDC-0449 (Week 116).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] Stage 2: New Formulation [GDC-0449 (150 mg )]
Hide Arm/Group Description Participants received single dose of GDC-0449 hard gelatin capsules at 150 mg on Day 1, thereafter Day 8 received daily until disease progression, maximum benefit, or intolerability. Stage 1: GDC-0449 (270 mg) Participants received single dose of GDC-0449 hard gelatin capsules at 270 mg on Day 1, thereafter Day 8 received daily dose until disease progression, maximum benefit, or intolerability. Participants received single dose of GDC-0449 hard gelatin capsules at 540 mg on Day 1, thereafter Day 8 received daily dose until disease progression, maximum benefit, or intolerability. Participants with basal cell carcinoma (BCC) received daily dose of GDC-0449 hard gelatin capsules at 150 mg on Day 1 until disease progression, maximum benefit, or intolerability. Participants with basal cell carcinoma (BCC) received daily dose of GDC-0449 hard gelatin capsules at 270 mg on Day 1 until disease progression, maximum benefit, or intolerability. Participants with tolerable safety, pharmacokinetic and pharmacodynamic data from Stage 1 received daily dose of GDC-0449 hard gelatin capsules at 150 mg on Day 1 until disease progression, maximum benefit, or intolerability. Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
All-Cause Mortality
Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] Stage 2: New Formulation [GDC-0449 (150 mg )]
Affected / at Risk (%) 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
Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] Stage 2: New Formulation [GDC-0449 (150 mg )]
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/7 (42.86%)   2/9 (22.22%)   1/4 (25.00%)   2/6 (33.33%)   4/14 (28.57%)   4/12 (33.33%)   4/16 (25.00%) 
Cardiac disorders               
Atrial fibrillation * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Gastrointestinal disorders               
Abdominal pain * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  2/12 (16.67%)  0/16 (0.00%) 
Duodenal ulcer * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Impaired gastric emptying * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Intestinal obstruction * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Vomiting * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
General disorders               
Pain * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Infections and infestations               
Infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Pneumonia * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Pyelonephritis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Injury, poisoning and procedural complications               
Transfusion reaction * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Metabolism and nutrition disorders               
Hyponatraemia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Hyperkalaemia * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Dehydration * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Pancreatic carcinoma metastatic * 1  1/7 (14.29%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Adenocarcinoma pancreas * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Pancreatic carcinoma * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Chondrosarcoma * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Basal cell carcinoma * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Nervous system disorders               
Presyncope * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Psychiatric disorders               
Paranoia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Confusional state * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Dyspnoea * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Vascular disorders               
Haemorrhage * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stage 1: GDC-0449 (150 mg) Stage 1: GDC-0449 (270 mg) Stage 1: GDC-0449 (540 mg) Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] Stage 2: New Formulation [GDC-0449 (150 mg )]
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/7 (100.00%)   9/9 (100.00%)   4/4 (100.00%)   6/6 (100.00%)   14/14 (100.00%)   12/12 (100.00%)   16/16 (100.00%) 
Blood and lymphatic system disorders               
Anaemia * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Leukopenia * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Lymph node pain * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Lymphopenia * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Neutropenia * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Thrombocytopenia * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Cardiac disorders               
Sinus tachycardia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Cardiac flutter * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Palpitations * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Pericardial effusion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Sinus bradycardia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Tachycardia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Ear and labyrinth disorders               
Tinnitus * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Auricular swelling * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Cerumen impaction * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Dysacusis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Ear canal stenosis * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Ear haemorrhage * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Ear pain * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Hyperacusis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Hypoacusis * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Eye disorders               
Vision blurred * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  2/16 (12.50%) 
Lacrimation increased * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Vitreous floaters * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Arcus lipoides * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Conjunctival hyperaemia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Dry eye * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Eye discharge * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Keratitis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Ocular hyperaemia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Photophobia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Photopsia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Pterygium * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Visual acuity reduced * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Gastrointestinal disorders               
Nausea * 1  1/7 (14.29%)  5/9 (55.56%)  1/4 (25.00%)  2/6 (33.33%)  5/14 (35.71%)  4/12 (33.33%)  5/16 (31.25%) 
Diarrhoea * 1  1/7 (14.29%)  2/9 (22.22%)  1/4 (25.00%)  3/6 (50.00%)  4/14 (28.57%)  1/12 (8.33%)  6/16 (37.50%) 
Constipation * 1  1/7 (14.29%)  1/9 (11.11%)  1/4 (25.00%)  3/6 (50.00%)  2/14 (14.29%)  2/12 (16.67%)  2/16 (12.50%) 
Vomiting * 1  1/7 (14.29%)  2/9 (22.22%)  1/4 (25.00%)  0/6 (0.00%)  2/14 (14.29%)  3/12 (25.00%)  2/16 (12.50%) 
Abdominal pain * 1  0/7 (0.00%)  2/9 (22.22%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  3/12 (25.00%)  2/16 (12.50%) 
Abdominal pain upper * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  3/14 (21.43%)  0/12 (0.00%)  3/16 (18.75%) 
Dyspepsia * 1  0/7 (0.00%)  2/9 (22.22%)  0/4 (0.00%)  0/6 (0.00%)  3/14 (21.43%)  2/12 (16.67%)  1/16 (6.25%) 
Abdominal distension * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  4/14 (28.57%)  1/12 (8.33%)  2/16 (12.50%) 
Dysphagia * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  3/14 (21.43%)  0/12 (0.00%)  1/16 (6.25%) 
Dry mouth * 1  1/7 (14.29%)  1/9 (11.11%)  0/4 (0.00%)  2/6 (33.33%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Gastrooesophageal reflux disease * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  2/16 (12.50%) 
Flatulence * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  2/16 (12.50%) 
Abdominal discomfort * 1  1/7 (14.29%)  2/9 (22.22%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Abdominal pain lower * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  1/16 (6.25%) 
Oral pain * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  1/16 (6.25%) 
Ascites * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Frequent bowel movements * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Abdominal rigidity * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Cheilitis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Duodenal ulcer * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Dyschezia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Eructation * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Faecal incontinence * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Gastric disorder * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Glossodynia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Haemorrhoidal haemorrhage * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Haemorrhoids * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Hyperchlorhydria * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Hypoaesthesia oral * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Inguinal hernia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Lip ulceration * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Mouth ulceration * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Mucous stools * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Oesophageal stenosis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Oesophagitis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Oral cavity fistula * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Oral mucosal blistering * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Tongue ulceration * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Tooth loss * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
General disorders               
Fatigue * 1  1/7 (14.29%)  4/9 (44.44%)  0/4 (0.00%)  4/6 (66.67%)  8/14 (57.14%)  6/12 (50.00%)  5/16 (31.25%) 
Pyrexia * 1  1/7 (14.29%)  0/9 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  3/14 (21.43%)  2/12 (16.67%)  0/16 (0.00%) 
Pain * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  3/14 (21.43%)  1/12 (8.33%)  2/16 (12.50%) 
Chest pain * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  3/14 (21.43%)  0/12 (0.00%)  2/16 (12.50%) 
Oedema peripheral * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  1/12 (8.33%)  3/16 (18.75%) 
Oedema * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  1/12 (8.33%)  1/16 (6.25%) 
Chest discomfort * 1  0/7 (0.00%)  2/9 (22.22%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Chills * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/14 (21.43%)  0/12 (0.00%)  1/16 (6.25%) 
Facial pain * 1  0/7 (0.00%)  1/9 (11.11%)  1/4 (25.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Influenza like illness * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/14 (14.29%)  0/12 (0.00%)  1/16 (6.25%) 
Gait disturbance * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Asthenia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Axillary pain * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Catheter site pain * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Catheter site related reaction * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Feeling cold * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Feeling hot * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Feeling jittery * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Puncture site haemorrhage * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Sensation of foreign body * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Unevaluable event * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Immune system disorders               
Drug hypersensitivity * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Seasonal allergy * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Infections and infestations               
Upper respiratory tract infection * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  3/14 (21.43%)  2/12 (16.67%)  2/16 (12.50%) 
Rhinitis * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  3/14 (21.43%)  0/12 (0.00%)  2/16 (12.50%) 
Influenza * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/14 (14.29%)  1/12 (8.33%)  0/16 (0.00%) 
Sinusitis * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  2/6 (33.33%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Nasopharyngitis * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Bronchitis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Diverticulitis * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Eye infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  1/16 (6.25%) 
Folliculitis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  1/16 (6.25%) 
Gastroenteritis viral * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  1/12 (8.33%)  0/16 (0.00%) 
Oral candidiasis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Pneumonia * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Wound infection staphylococcal * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Wound infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Abscess limb * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Candidiasis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Catheter site infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Cystitis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Gastroenteritis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Infected cyst * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Lobar pneumonia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Localised infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Onychomycosis * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Oral fungal infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Oral herpes * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Postoperative wound infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Rash pustular * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Skin infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Urinary tract infection * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Injury, poisoning and procedural complications               
Contusion * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Excoriation * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Laceration * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Wound secretion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Corneal abrasion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Humerus fracture * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Muscle rupture * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Spinal compression fracture * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Tooth fracture * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Wound complication * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Investigations               
Weight decreased * 1  0/7 (0.00%)  3/9 (33.33%)  1/4 (25.00%)  2/6 (33.33%)  4/14 (28.57%)  2/12 (16.67%)  6/16 (37.50%) 
Blood alkaline phosphatase increased * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  1/16 (6.25%) 
Blood chloride decreased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  1/12 (8.33%)  0/16 (0.00%) 
Lymphocyte count decreased * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Alanine aminotransferase increased * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Aspartate aminotransferase increased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Blood lactate dehydrogenase increased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Blood urea increased * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Weight increased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  1/16 (6.25%) 
Blood bilirubin increased * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Blood creatinine increased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Blood potassium increased * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Blood triglycerides increased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Blood urine * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Blood urine present * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Brain natriuretic peptide increased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Carbohydrate antigen 19-9 increased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Electrocardiogram change * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Haemoglobin decreased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Metamyelocyte percentage increased * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Myelocyte percentage increased * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Neutrophil count decreased * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Metabolism and nutrition disorders               
Decreased appetite * 1  0/7 (0.00%)  4/9 (44.44%)  2/4 (50.00%)  1/6 (16.67%)  4/14 (28.57%)  5/12 (41.67%)  3/16 (18.75%) 
Hyponatraemia * 1  3/7 (42.86%)  1/9 (11.11%)  0/4 (0.00%)  2/6 (33.33%)  2/14 (14.29%)  1/12 (8.33%)  0/16 (0.00%) 
Hypokalaemia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  2/12 (16.67%)  3/16 (18.75%) 
Hypomagnesaemia * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  2/6 (33.33%)  2/14 (14.29%)  1/12 (8.33%)  1/16 (6.25%) 
Dehydration * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  2/16 (12.50%) 
Hyperglycaemia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  1/14 (7.14%)  1/12 (8.33%)  0/16 (0.00%) 
Hypoalbuminaemia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  0/14 (0.00%)  1/12 (8.33%)  1/16 (6.25%) 
Hypercholesterolaemia * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  1/6 (16.67%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Hyperkalaemia * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Hypoglycaemia * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Electrolyte imbalance * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Fluid retention * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Gout * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Hypercalcaemia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Hypertriglyceridaemia * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Hypocalcaemia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Salt craving * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Type 2 diabetes mellitus * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Musculoskeletal and connective tissue disorders               
Muscle spasms * 1  2/7 (28.57%)  2/9 (22.22%)  1/4 (25.00%)  4/6 (66.67%)  12/14 (85.71%)  0/12 (0.00%)  11/16 (68.75%) 
Back pain * 1  1/7 (14.29%)  2/9 (22.22%)  1/4 (25.00%)  2/6 (33.33%)  1/14 (7.14%)  2/12 (16.67%)  4/16 (25.00%) 
Musculoskeletal chest pain * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  3/14 (21.43%)  1/12 (8.33%)  2/16 (12.50%) 
Arthralgia * 1  1/7 (14.29%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  1/12 (8.33%)  2/16 (12.50%) 
Pain in extremity * 1  0/7 (0.00%)  3/9 (33.33%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  2/16 (12.50%) 
Musculoskeletal pain * 1  1/7 (14.29%)  3/9 (33.33%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  1/12 (8.33%)  0/16 (0.00%) 
Flank pain * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  0/14 (0.00%)  1/12 (8.33%)  2/16 (12.50%) 
Myalgia * 1  0/7 (0.00%)  2/9 (22.22%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Muscle tightness * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  1/16 (6.25%) 
Muscle twitching * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Neck pain * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Joint swelling * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Musculoskeletal discomfort * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Pain in jaw * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Arthritis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Groin pain * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Intervertebral disc protrusion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Joint range of motion decreased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Joint stiffness * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Musculoskeletal stiffness * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Osteopenia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Bowen’s disease * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Neoplasm malignant * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Seborrhoeic keratosis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Skin neoplasm bleeding * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Skin papilloma * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Tumour associated fever * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Nervous system disorders               
Dysgeusia * 1  1/7 (14.29%)  3/9 (33.33%)  1/4 (25.00%)  5/6 (83.33%)  8/14 (57.14%)  2/12 (16.67%)  8/16 (50.00%) 
Hypoaesthesia * 1  0/7 (0.00%)  0/9 (0.00%)  3/4 (75.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  2/16 (12.50%) 
Headache * 1  0/7 (0.00%)  1/9 (11.11%)  1/4 (25.00%)  1/6 (16.67%)  2/14 (14.29%)  0/12 (0.00%)  1/16 (6.25%) 
Dizziness * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  1/12 (8.33%)  1/16 (6.25%) 
Paraesthesia * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  1/16 (6.25%) 
Sinus headache * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Somnolence * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Ageusia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  2/16 (12.50%) 
Anosmia * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Neuropathy peripheral * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  1/12 (8.33%)  0/16 (0.00%) 
Tremor * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Amimia * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Burning sensation * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Carotid artery stenosis * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Cognitive disorder * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Dyskinesia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Hyperaesthesia * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Hypogeusia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Memory impairment * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Neuralgia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Paresis cranial nerve * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Parosmia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Phantom pain * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Sensory disturbance * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Tongue paralysis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Trigeminal neuralgia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Viith nerve paralysis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Psychiatric disorders               
Anxiety * 1  1/7 (14.29%)  2/9 (22.22%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  1/12 (8.33%)  4/16 (25.00%) 
Insomnia * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  3/14 (21.43%)  0/12 (0.00%)  4/16 (25.00%) 
Depression * 1  1/7 (14.29%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  1/12 (8.33%)  1/16 (6.25%) 
Abnormal dreams * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Hallucination * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Sleep disorder * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Stress * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Renal and urinary disorders               
Urinary hesitation * 1  0/7 (0.00%)  0/9 (0.00%)  2/4 (50.00%)  2/6 (33.33%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Dysuria * 1  0/7 (0.00%)  2/9 (22.22%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Haematuria * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  1/12 (8.33%)  0/16 (0.00%) 
Chromaturia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Hydronephrosis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Pollakiuria * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Proteinuria * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Renal pain * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Urinary retention * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Urine flow decreased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Reproductive system and breast disorders               
Amenorrhoea * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Breast swelling * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Menstruation irregular * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Cough * 1  1/7 (14.29%)  2/9 (22.22%)  1/4 (25.00%)  2/6 (33.33%)  5/14 (35.71%)  2/12 (16.67%)  2/16 (12.50%) 
Dyspnoea * 1  2/7 (28.57%)  1/9 (11.11%)  0/4 (0.00%)  2/6 (33.33%)  2/14 (14.29%)  3/12 (25.00%)  3/16 (18.75%) 
Productive cough * 1  1/7 (14.29%)  1/9 (11.11%)  0/4 (0.00%)  2/6 (33.33%)  1/14 (7.14%)  1/12 (8.33%)  1/16 (6.25%) 
Dyspnoea exertional * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  2/12 (16.67%)  0/16 (0.00%) 
Oropharyngeal pain * 1  0/7 (0.00%)  1/9 (11.11%)  1/4 (25.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  1/16 (6.25%) 
Rhinorrhoea * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  1/12 (8.33%)  0/16 (0.00%) 
Dysphonia * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  2/14 (14.29%)  0/12 (0.00%)  1/16 (6.25%) 
Respiratory tract congestion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  2/14 (14.29%)  0/12 (0.00%)  0/16 (0.00%) 
Wheezing * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  0/12 (0.00%)  1/16 (6.25%) 
Pleuritic pain * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Sinus congestion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Throat irritation * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Aspiration * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Atelectasis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Epistaxis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Haemoptysis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Hydrothorax * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Nasal congestion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Oropharyngeal swelling * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Pleural effusion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Pleurisy * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Sputum increased * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
upper respiratory tract congestion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Upper−airway cough syndrome * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Skin and subcutaneous tissue disorders               
Alopecia * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  3/6 (50.00%)  10/14 (71.43%)  1/12 (8.33%)  9/16 (56.25%) 
Pruritus * 1  1/7 (14.29%)  2/9 (22.22%)  1/4 (25.00%)  2/6 (33.33%)  1/14 (7.14%)  0/12 (0.00%)  2/16 (12.50%) 
Erythema * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  4/14 (28.57%)  0/12 (0.00%)  1/16 (6.25%) 
Dry skin * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  2/6 (33.33%)  1/14 (7.14%)  0/12 (0.00%)  2/16 (12.50%) 
Rash * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  3/14 (21.43%)  0/12 (0.00%)  1/16 (6.25%) 
Skin exfoliation * 1  0/7 (0.00%)  2/9 (22.22%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Acne * 1  0/7 (0.00%)  0/9 (0.00%)  1/4 (25.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Decubitus ulcer * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Dermatitis acneiform * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Hyperhidrosis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  1/16 (6.25%) 
Madarosis * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Night sweats * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Skin discolouration * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Skin ulcer * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Actinic elastosis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Campbell de morgan spots * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
hair colour changes * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Nail ridging * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Onychoclasis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Pain of skin * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Photosensitivity reaction * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Pruritus generalised * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Psoriasis * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/12 (8.33%)  0/16 (0.00%) 
Rash macular * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Rash maculo−papular * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Rash pruritic * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Skin lesion * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Skin tightness * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Swelling face * 1  0/7 (0.00%)  1/9 (11.11%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Urticaria * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/12 (0.00%)  0/16 (0.00%) 
Vascular disorders               
Flushing * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  3/14 (21.43%)  0/12 (0.00%)  1/16 (6.25%) 
Hypertension * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  1/14 (7.14%)  1/12 (8.33%)  1/16 (6.25%) 
Hypotension * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  2/12 (16.67%)  2/16 (12.50%) 
Deep vein thrombosis * 1  1/7 (14.29%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Hot flush * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
Orthostatic hypotension * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  1/6 (16.67%)  0/14 (0.00%)  0/12 (0.00%)  0/16 (0.00%) 
Raynaud’s phenomenon * 1  0/7 (0.00%)  0/9 (0.00%)  0/4 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/12 (0.00%)  1/16 (6.25%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00607724     History of Changes
Obsolete Identifiers: NCT00862771
Other Study ID Numbers: CDR0000585468
JHOC-J06131
GENETECH-SHH3925g
First Submitted: January 31, 2008
First Posted: February 6, 2008
Results First Submitted: July 22, 2015
Results First Posted: October 8, 2015
Last Update Posted: October 8, 2015