Download PDF

Clinical Trial Results:
A Randomized, Double-Blind Phase 2 Study Comparing Gemcitabine and Cisplatin in Combination with OGX-427 or Placebo in Patients with Advanced Transitional Cell Carcinoma

Summary
EudraCT number	2011-002424-41
Trial protocol	DE ES IT
Global end of trial date	20 Nov 2014

Results information
Results version number	v1(current)
This version publication date	07 Jul 2016
First version publication date	07 Jul 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

OGX-427-02

ISRCTN number

US NCT number

NCT01454089

WHO universal trial number (UTN)

Sponsor organisation name

OncoGenex Technologies Inc

Sponsor organisation address

1001 W Broadway, Suite 400, Vancouver, BC, Canada, V6H 4B1

Public contact

Director, Regulatory Affairs, OncoGenex Technologies Inc , 001 425-686-1500,

Scientific contact

Director, Regulatory Affairs, OncoGenex Technologies Inc , 001 425-686-1500,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

20 Nov 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Nov 2014

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study is to ascertain whether there is evidence of longer survival relative to the control arm for three comparisons: 600 mg OGX-427 arm to control arm; 1000 mg OGX-427 arm to control arm; and pooled 600 mg and 1000 mg OGX-427 arms to control arm.

Protection of trial subjects

Each subject was provided an informed consent form that was reviewed and approved by the site’s governing Institutional Review Board (IRB), Research Ethics Board (REB) or Ethics Committee (EC). The Principal Investigator (or designee) provided potential subjects with a verbal description of the study, including but not limited to, study purpose and study procedures, risks and benefits and answered all subject questions prior to signing the form. Because Grade 1 and 2 constitutional symptoms (e.g. chills, fever, pruritus, flushing) are seen in the majority of patients during the loading-dose infusions, all subjects were premedicated with an H2 blocker, antihistamine and corticosteroid during the loading doses and Cycle 1, (Days 1, 8 and 15), at a minimum.

Background therapy

Subjects received gemcitabine (1000 mg/m2) administered IV on Days 1 and 8 of each 21-day cycle following Study Drug infusion. Following the administration of gemcitabine on Day 1, cisplatin (70 mg/m2) was administered IV. Carboplatin could be substituted for cisplatin for some unacceptable toxicities. The Cycle 1, Day 1 administration of chemotherapy must have occurred within 5 days of the third loading dose of Study Drug. Chemotherapy treatment on this schedule continued for up to six cycles or until disease progression or unacceptable toxicity.

Evidence for comparator

Actual start date of recruitment

01 Oct 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 24

Country: Number of subjects enrolled

France: 23

Country: Number of subjects enrolled

Germany: 16

Country: Number of subjects enrolled

Italy: 7

Country: Number of subjects enrolled

Poland: 28

Country: Number of subjects enrolled

Spain: 37

Country: Number of subjects enrolled

United States: 44

Worldwide total number of subjects

179

EEA total number of subjects

111

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

This study included a 28-day Screening period. Of the 256 subjects screened, 3 died, 59 did not meet inclusion/exclusion criteria, and 11 withdrew consent. Of the 183 subjects randomized, 179 received at least 1 dose of study drug.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo + Gem/Cis

Arm description

Subjects received 3 loading doses of placebo within a 9-day period. Following the loading dose period, participants received weekly placebo infusions intravenously (IV) on Days 1, 8 and 15 of each 21-day cycle. Subjects received chemotherapy consisting of up to 6 cycles of gemcitabine (1000 mg/m^2 IV on Days 1 and 8) and cisplatin (70 mg/m^2 IV on Day 1).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received each dose of Study Drug as a 2-hour infusion.

OGX-427 600 mg + Gem/Cis

Arm description

Subjects received 3 loading doses of 600 mg OGX-427 within a 9-day period. Following the loading dose period, subjects received weekly OGX-427 infusions (600 mg IV) on Days 1, 8 and 15 of each 21-day cycle. Subjects received chemotherapy consisting of up to 6 cycles of gemcitabine (1000 mg/m^2 IV on Days 1 and 8) and cisplatin (70 mg/m^2 IV on Day 1).

Arm type

Experimental

Investigational medicinal product name

OGX-427

Investigational medicinal product code

OGX-427

Other name

apatorsen

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received each dose of Study Drug as a 2-hour infusion.

OGX-427 1000 mg + Gem/Cis

Arm description

Subjects received 3 loading doses of 600 mg OGX-427 within a 9-day period. Following the loading dose period, subjects received weekly OGX-427 infusions (1000 mg IV) on Days 1, 8 and 15 of each 21-day cycle. Subjects received chemotherapy consisting of up to 6 cycles of gemcitabine (1000 mg/m^2 IV on Days 1 and 8) and cisplatin (70 mg/m^2 IV on Day 1).

Arm type

Experimental

Investigational medicinal product name

OGX-427

Investigational medicinal product code

OGX-427

Other name

apatorsen

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received each dose of Study Drug as a 2-hour infusion.

Number of subjects in period 1	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis
Started	61	58	60
Entered Chemotherapy Period	60	55	56
Completed 6 Cycles of Chemotherapy	21 ^[1]	21 ^[2]	12 ^[3]
Entered Maintenance Period	38 ^[4]	33	28 ^[5]
Completed	39	29	35
Not completed	22	29	25
Consent withdrawn by subject	1	3	3
Study Terminated by Sponsor	20	23	22
Lost to follow-up	1	3	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: 21 subjects completed all 6 cycles of chemotherapy.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: 21 subjects completed all 6 cycles of chemotherapy.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: 12 subjects completed all 6 cycles of chemotherapy.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: 38 subjects entered the maintenance period (not all completed 6 cycles of chemotherapy).
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: 28 subjects entered the maintenance period (not all completed 6 cycles of chemotherapy).

Baseline characteristics

Top of page

Reporting group title

Placebo + Gem/Cis

Reporting group description

Reporting group title

OGX-427 600 mg + Gem/Cis

Reporting group description

Reporting group title

OGX-427 1000 mg + Gem/Cis

Reporting group description

Reporting group values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total
Number of subjects	61	58	60	179
Age, Customized
Units: participants
< 65 Years	32	25	35	92
≥ 65 Years	29	33	25	87
Age Continuous
Units: years
arithmetic mean (standard deviation)	62.7 ± 9.2	65 ± 6.5	63.4 ± 8.9	-
Gender, Male/Female
Units: participants
Female	9	7	15	31
Male	52	51	45	148
Karnofsky Performance Status (KPS)
KPS quantifies a participant's general well-being and activities of daily life and participants were classified based on their functional impairment. An 11-level score, KPS score ranges between 0 (death) to 100 (no evidence of disease) percent. Higher score means higher ability to perform daily tasks.
Units: Subjects
≥ 80%	55	53	54	162
< 80%	6	5	6	17
Visceral Disease
Presence of visceral metastases (defined as documented disease in lung, liver, and/or bone).
Units: Subjects
No	18	25	18	61
Yes	43	33	42	118
Baseline Circulating Tumor Cell (CTC) Count
Participants with a baseline assessment (n=45, 45, 48 for the 3 arms, respectively).
Units: Subjects
0 cells	28	26	27	81
1 to < 5 cells	5	11	8	24
5 to 20 cells	6	5	5	16
21 to 50 cells	5	2	2	9
> 50 cells	1	1	6	8
No assessment	16	13	12	41
Age, Customized
Units: Subjects
< 75 Years	55	56	54	165
≥ 75 Years	6	2	6	14

End points

Top of page

Reporting group title

Placebo + Gem/Cis

Reporting group description

Reporting group title

OGX-427 600 mg + Gem/Cis

Reporting group description

Reporting group title

OGX-427 1000 mg + Gem/Cis

Reporting group description

Subject analysis set title

Total OGX-427 + Gem/Cis

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received 3 loading doses of 600 mg OGX-427 within a 9-day period. Following the loading dose period, participants received weekly OGX-427 infusions (600 mg or 1000 mg IV) on Days 1, 8 and 15 of each 21-day cycle. Participants received chemotherapy consisting of up to 6 cycles of gemcitabine (1000 mg/m^2 IV on Days 1 and 8) and cisplatin (70 mg/m^2 IV on Day 1).

Primary: Overall Survival (OS)

Top of page

End point title

Overall Survival (OS)

End point description

OS is defined as the time from randomization to death from any cause; OS was censored on date of last contact for participants still alive at the time of analysis.

End point type

Primary

End point timeframe

Baseline to date of death by any cause (up to approximately 3 years)

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61	58	60	118
Units: days
median (confidence interval 95%)	456 (357 to 589)	467 (326 to 705)	474 (350 to 583)	474 (362 to 674)

Statistical Analysis 1

Comparison groups

Placebo + Gem/Cis v OGX-427 600 mg + Gem/Cis

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.252 ^[1]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.856

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.355

Notes
[1] - One-sided p-value from stratified log-rank tests.

Statistical Analysis 2

Comparison groups

Placebo + Gem/Cis v OGX-427 1000 mg + Gem/Cis

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.32 ^[2]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.898

Confidence interval

level

95%

sides

2-sided

lower limit

0.572

upper limit

1.41

Notes
[2] - One-sided p-value from stratified log-rank tests.

Statistical Analysis 3

Comparison groups

Placebo + Gem/Cis v Total OGX-427 + Gem/Cis

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.234 ^[3]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.867

Confidence interval

level

95%

sides

2-sided

lower limit

0.588

upper limit

1.277

Notes
[3] - One-sided p-value from stratified log-rank tests.

Secondary: Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs (SAEs), and Grade 3 or Higher AEs

Top of page

End point title

Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs (SAEs), and Grade 3 or Higher AEs

End point description

AE=any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the administration, at any dose, of study drug, whether or not considered related to that product. SAE=any untoward medical occurrence that (at any dose): results in death; is life-threatening; requires inpatient hospital admission or prolongs existing hospitalization; results in persistent or significant disability/incapacity; results in congenital anomaly/birth defect; or other important medical event. Treatment-emergent AEs=AE that occurred after the first dose of study drug up to 30 days after the last dose of study drug. AEs were graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment-emergent AEs could have occurred during loading dose period, chemotherapy period, maintenance period, and treatment period A detailed summary of adverse events is located in the Reported Adverse Event Module.

End point type

Secondary

End point timeframe

From first dose of study drug to 30 days after last dose of study drug (safety reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61	58	60	118
Units: participants
number (not applicable)
Treatment-emergent AE	61	58	60	118
Treatment-emergent SAE	26	31	37	68
Treatment-emergent AE Grade 3 or Higher	54	54	58	112

No statistical analyses for this end point

Secondary: Number of Participants With at ≥ 1 Hematology Abnormality and ≥ 1 Grade 3 or Higher Hematology Abnormality

Top of page

End point title

Number of Participants With at ≥ 1 Hematology Abnormality and ≥ 1 Grade 3 or Higher Hematology Abnormality

End point description

Hematology abnormalities occurring after the first dose of study drug. Multiple occurrences of an event within a subject were counted only once, as the highest grade. Toxicity grading based on the NCI-CTCAE, Version 4.0.

End point type

Secondary

End point timeframe

From first dose of study drug to 30 days after last dose of study drug (safety reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61	58	60	118
Units: participants
number (not applicable)
Any Abnormality	61	56	58	114
Any Grade 3 or Higher Abnormality	39	45	51	96
Anemia	61	56	58	114
Grade 3 or Higher Anemia	23	24	28	52
Leukopenia	47	43	48	91
Grade 3 or Higher Leukopenia	17	17	25	42
Lymphopenia	43	46	44	90
Grade 3 or Higher Lymphopenia	16	15	19	34
Neutropenia	46	39	44	83
Grade 3 or Higher Neutropenia	26	28	34	62
Thrombocytopenia	45	39	45	84
Grade 3 or Higher Thrombocytopenia	13	17	22	39

No statistical analyses for this end point

Secondary: Number of Participants With ≥ 1 Serum Chemistry Laboratory Abnormality and ≥ 1 Grade 3 or Higher Serum Chemistry Laboratory Abnormality

Top of page

End point title

Number of Participants With ≥ 1 Serum Chemistry Laboratory Abnormality and ≥ 1 Grade 3 or Higher Serum Chemistry Laboratory Abnormality

End point description

Chemistry laboratory abnormalities occurring after the first dose of study drug. Multiple occurrences of an event within a participant were counted only once, as the highest grade. Toxicity grading based on NCI-CTCAE, Version 4.0. 'Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT)' is a derived parameter, and includes participants with elevations in ALT or AST or both.

End point type

Secondary

End point timeframe

From first dose of study drug to 30 days after last dose of study drug (safety reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61	58	60	118
Units: participants
number (not applicable)
Any Abnormality	60	56	58	114
Any Grade 3 or Higher Abnormality	36	35	30	65
Elevated ALT	33	31	29	60
Grade 3 or Higher Elevated ALT	2	1	1	2
Elevated AST	27	15	20	35
Grade 3 or Higher Elevated AST	1	2	1	3
Elevated AST or ALT	39	33	32	65
Grade 3 or Higher Elevated AST or ALT	2	2	1	3
Elevated Alkaline Phosphatase	25	26	28	54
Grade 3 or Higher Elevated Alkaline Phosphatase	3	1	1	2
Elevated Creatinine	27	37	38	75
Grade 3 or Higher Elevated Creatinine	2	3	2	5
Hyperbilirubinemia	8	6	4	10
Grade 3 or Higher Hyperbilirubinemia	0	3	0	3
Hypercalcemia	16	20	13	33
Grade 3 or Higher Hypercalcemia	1	0	0	0
Hyperkalemia	30	22	21	43
Grade 3 or Higher Hyperkalemia	4	1	2	3
Hypermagnesemia	3	7	6	13
Grade 3 or Higher Hypermagnesemia	0	0	1	1
Hypernatremia	4	2	2	4
Grade 3 or Higher Hypernatremia	0	0	0	0
Hyperuricemia	27	18	20	38
Grade 3 or Higher Hyperuricemia	27	18	20	38
Hypoalbuminemia	36	36	40	76
Grade 3 or Higher Hypoalbuminemia	1	3	1	4
Hypocalcemia	24	19	23	42
Grade 3 or Higher Hypocalcemia	3	1	0	1
Hypokalemia	14	15	17	32
Grade 3 or Higher Hypokalemia	5	6	3	9
Hypomagnesemia	31	32	34	66
Grade 3 or Higher Hypomagnesemia	2	1	3	4
Hyponatremia	42	42	42	84
Grade 3 or Higher Hyponatremia	4	11	12	23
Hypophosphatemia	27	25	23	48
Grade 3 or Higher Hypophosphatemia	3	5	3	8

No statistical analyses for this end point

Secondary: Number of Participants With ≥ 1 Urinalysis Abnormality

Top of page

End point title

Number of Participants With ≥ 1 Urinalysis Abnormality

End point description

Urinalysis abnormalities occurring after the first dose of study drug. Multiple occurrences of an event within a participant were counted only once, as the highest grade. Each '+' indicates a higher order of magnitude of abnormal protein present in the urine.

End point type

Secondary

End point timeframe

From first dose of study drug to 30 days after last dose of study drug (safety reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61	58	60	118
Units: participants
number (not applicable)
Any Abnormality	56	57	57	114
Erythrocytes, Any	51	52	53	105
Erythrocytes, Trace	16	16	11	27
Erythrocytes, Moderate	19	22	14	36
Erythrocytes, Large	16	14	28	42
Protein, Any	50	51	49	100
Protein, Trace	7	9	9	18
Protein, +	21	20	21	41
Protein, ++	13	15	11	26
Protein, +++	8	5	5	10
Protein, ++++	1	2	3	5

No statistical analyses for this end point

Secondary: Confirmed Best Objective Tumor Response

Top of page

End point title

Confirmed Best Objective Tumor Response

End point description

Complete Response (CR)=complete disappearance of all measurable and non-measurable disease with no new lesions. Any pathological lymph node (target or non-target) must have a reduction in short axis to < 10 mm). All markers of disease must have normalized. Partial Response (PR)=a decrease from baseline of ≥ 30% of the diameter(s) of all target measurable lesions with no unequivocal progression of non-measurable lesions and no new lesions. Stable Disease (SD)=does not qualify for CR, PR, or progression. Disease Progression (PD)=if at least one of following criteria is met: appearance of any new lesion or site of disease; a 20% increase in the sum of the diameter(s) of target measurable lesions over either the smallest sum observed or over baseline if no decrease during therapy has occurred (the sum must also demonstrate an absolute increase of at least 5 mm); or unequivocal progression of non-target lesions alone.

End point type

Secondary

End point timeframe

Baseline to measured progressive disease (up to approximately 3 years)

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61	58	60	118
Units: participants
number (not applicable)
CR	4	5	7	12
PR	33	28	23	51
SD	11	11	13	24
PD	9	11	9	20
Not Done	4	3	8	11

No statistical analyses for this end point

Secondary: Overall Response Rate (ORR) and Disease Control Rate

Top of page

End point title

Overall Response Rate (ORR) and Disease Control Rate

End point description

Participants were defined as having an “overall response” if their best response was either confirmed CR, confirmed PR, unconfirmed CR or unconfirmed PR. ORR was defined as the percent of participants who had an overall response. Participants were defined as having “disease control” if their best response was confirmed CR, confirmed PR, unconfirmed CR, unconfirmed PR or SD. The disease control rate (DCR) was defined as the percent of participants with disease control. (See “Best Objective Tumor Response” Outcome Measure above for response category definitions.)

End point type

Secondary

End point timeframe

Baseline to measured progressive disease (up to approximately 3 years)

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61	58	60	118
Units: percentage of participants
number (not applicable)
Overall Response Rate	61	57	50	53
Disease Control Rate	79	76	72	74

Statistical Analysis 1

Statistical analysis description

Overall Response Rate

Comparison groups

Placebo + Gem/Cis v OGX-427 600 mg + Gem/Cis

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3513

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.51

Statistical Analysis 2

Statistical analysis description

Overall Response Rate

Comparison groups

Placebo + Gem/Cis v OGX-427 1000 mg + Gem/Cis

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2542

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

1.37

Statistical Analysis 3

Comparison groups

Placebo + Gem/Cis v Total OGX-427 + Gem/Cis

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2353

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

1.29

Statistical Analysis 4

Statistical analysis description

Disease Control Rate

Comparison groups

Placebo + Gem/Cis v OGX-427 600 mg + Gem/Cis

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4129

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

1.75

Statistical Analysis 5

Statistical analysis description

Disease Control Rate

Comparison groups

Placebo + Gem/Cis v OGX-427 1000 mg + Gem/Cis

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3951

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

1.63

Statistical Analysis 6

Statistical analysis description

Disease Control Rate

Comparison groups

Placebo + Gem/Cis v Total OGX-427 + Gem/Cis

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.381

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.54

Secondary: Duration of ORR

Top of page

End point title

Duration of ORR

End point description

Duration of response is defined as the duration from the first overall response to the first event of SD or PD, whichever happened first. (See “Best Objective Tumor Response” Outcome Measure above for response category definitions.) If no SD or PD, the participant was censored at the last tumor assessment (prior to other anti-cancer therapy if applicable).

End point type

Secondary

End point timeframe

Baseline to measured progressive disease (up to approximately 3 years)

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	37 ^[4]	33 ^[5]	28 ^[6]	61 ^[7]
Units: days
median (confidence interval 95%)	156 (112 to 254)	259 (140 to 357)	218 (154 to 342)	245 (173 to 299)

Notes
[4] - subjects with an overall response
[5] - subjects with an overall response
[6] - subjects with an overall response
[7] - subjects with an overall response

No statistical analyses for this end point

Secondary: Progression-free Survival (PFS)

Top of page

End point title

Progression-free Survival (PFS)

End point description

PFS was defined as the time from randomization to the date of disease progression or death, whichever occurred first, before or after treatment discontinuation. For participants still on study and those who remained alive and had not progressed after treatment discontinuation, PFS was censored on the date of the last tumor assessment.

End point type

Secondary

End point timeframe

Baseline to measured progressive disease (up to approximately 12 months)

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61 ^[8]	58 ^[9]	60 ^[10]	118 ^[11]
Units: days
median (confidence interval 95%)	189 (148 to 242)	227 (183 to 301)	228 (150 to 270)	227 (183 to 252)

Notes
[8] - Number of subjects with progression or death=49
[9] - Number of subjects with progression or death=40
[10] - Number of subjects with progression or death=40
[11] - Number of subjects with progression or death=80

Statistical Analysis 1

Comparison groups

Placebo + Gem/Cis v OGX-427 600 mg + Gem/Cis

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.198

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.539

upper limit

1.278

Statistical Analysis 2

Comparison groups

Placebo + Gem/Cis v OGX-427 1000 mg + Gem/Cis

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.366

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.927

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.433

Statistical Analysis 3

Comparison groups

Placebo + Gem/Cis v Total OGX-427 + Gem/Cis

Number of subjects included in analysis

179

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.222

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.867

Confidence interval

level

95%

sides

2-sided

lower limit

0.601

upper limit

1.251

Secondary: Change From Baseline in Serum Hsp27 levels by End of Treatment

Top of page

End point title

Change From Baseline in Serum Hsp27 levels by End of Treatment

End point description

Post-baseline observations that did not have a corresponding baseline observation were excluded. End-of-treatment is last non-hemolyzed observation up to last dose + 30 days. Hemolyzed samples were excluded.

End point type

Secondary

End point timeframe

Baseline to 30 days after last dose of study drug (reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	58 ^[12]	53 ^[13]	56 ^[14]	109 ^[15]
Units: µg/L
arithmetic mean (standard deviation)
Baseline	8.6 ± 8.3	10.5 ± 13.4	9.9 ± 12.5	10.2 ± 12.9
Minimum Post-baseline Value	4.3 ± 4.7	5.4 ± 10.9	4.1 ± 5.1	4.7 ± 8.5
Change From Baseline	-4.3 ± 8	-5.1 ± 13.6	-5.8 ± 13.5	-5.5 ± 13.5

Notes
[12] - Subjects with an assessment
[13] - Subjects with an assessment
[14] - Subjects with an assessment
[15] - Subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Baseline in Serum Clusterin Levels by End of Treatment

Top of page

End point title

Change From Baseline in Serum Clusterin Levels by End of Treatment

End point description

Post-baseline observations that did not have a corresponding Baseline observation were excluded. End of Treatment is last observation up to last dose + 30 days.

End point type

Secondary

End point timeframe

Baseline to 30 days after last dose of study drug (reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	57 ^[16]	52 ^[17]	54 ^[18]	106 ^[19]
Units: mg/L
arithmetic mean (standard deviation)
Baseline	54.7 ± 22.5	56.7 ± 18.9	52 ± 10.5	54.3 ± 15.3
Minimum Post-baseline Value	43.2 ± 9	44.4 ± 9.3	48.2 ± 10.5	46.3 ± 10.1
Change From Baseline	-11.5 ± 21.8	-12.3 ± 18.9	-3.9 ± 9.8	-8 ± 15.5

Notes
[16] - Subjects with an assessment
[17] - Subjects with an assessment
[18] - Subjects with an assessment
[19] - Subjects with an assessment

No statistical analyses for this end point

Secondary: Baseline to Last Post-baseline Shift in Circulating Tumor Cell (CTC) Count

Top of page

End point title

Baseline to Last Post-baseline Shift in Circulating Tumor Cell (CTC) Count

End point description

Number of participants with baseline to last post-baseline shifts in 1 of 4 categories: from < 5 cells/7.5 mL at baseline to < 5 cells/7.5 mL at last post-baseline; from < 5 cells/7.5 mL at baseline to ≥ 5 cells/7.5 mL at last post baseline; from ≥ 5 cells/7.5 mL at baseline to < 5 cells/7.5 mL at last post-baseline; or from ≥ 5 cells/7.5 mL at baseline to ≥ 5 cells/7.5 mL at last post baseline.

End point type

Secondary

End point timeframe

Baseline to end of treatment (reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	40 ^[20]	38 ^[21]	38 ^[22]	76 ^[23]
Units: cells/7.5 mL
number (not applicable)
< 5 cells/7.5 mL to < 5 cells/7.5 mL	28	30	28	58
< 5 cells/7.5 mL to ≥ 5 cells/7.5 mL	2	2	0	2
≥ 5 cells/7.5 mL to < 5 cells/7.5 mL	7	5	10	15
≥ 5 cells/7.5 mL to ≥ 5 cells/7.5 mL	3	1	0	1

Notes
[20] - Subjects with both a baseline and end-of-treatment (last on-treatment observation) result
[21] - Subjects with both a baseline and end-of-treatment (last on-treatment observation) result
[22] - Subjects with both a baseline and end-of-treatment (last on-treatment observation) result
[23] - Subjects with both a baseline and end-of-treatment (last on-treatment observation) result

No statistical analyses for this end point

Secondary: Baseline to Last Post-baseline Change in CTC Count

Top of page

End point title

Baseline to Last Post-baseline Change in CTC Count

End point description

Number of participants with baseline to last post-baseline changes in 1 of 3 categories: Decrease from baseline; Increase from baseline, No change from baseline.

End point type

Secondary

End point timeframe

Baseline to end of treatment (reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	40 ^[24]	38 ^[25]	38 ^[26]	76 ^[27]
Units: cells/7.5 mL
number (not applicable)
Decrease	13	12	15	27
Increase	8	11	2	13
No change	19	15	21	36

Notes
[24] - Subjects with both a baseline and end-of-treatment (last on-treatment observation) result
[25] - Subjects with both a baseline and end-of-treatment (last on-treatment observation) result
[26] - Subjects with both a baseline and end-of-treatment (last on-treatment observation) result
[27] - Subjects with both a baseline and end-of-treatment (last on-treatment observation) result

No statistical analyses for this end point

Secondary: Serum OGX-427 Maximum Plasma Concentration (Cmax) and Trough Levels

Top of page

End point title

Serum OGX-427 Maximum Plasma Concentration (Cmax) and Trough Levels

End point description

EOT=end-of-treatment

End point type

Secondary

End point timeframe

Baseline to 30 days after last dose of study drug (reporting period ranged from approximately 30 days to 850 days).

End point values	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Number of subjects analysed	61 ^[28]	58 ^[29]	60 ^[30]	118 ^[31]
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1: Trough; n=51, 45, 46, 91	0.5 ± 3.2	36 ± 32	32.6 ± 25.5	34.3 ± 28.8
Cycle 1 Day 1: Cmax; n=50, 46, 39, 85	0.7 ± 4.8	62788.6 ± 34408.1	100526.2 ± 52571.8	80103.5 ± 47353.5
Cycle 2 Day 1: Trough; n=42, 41, 34, 75	0 ± 0	28.7 ± 23.7	27.6 ± 12.7	28.2 ± 19.4
Cycle 2 Day 1: Cmax; n=40, 33, 31, 64	0 ± 0	77830.9 ± 34463	103200 ± 25588.7	90119.1 ± 32838.5
Cycle 3 Day 1: Trough; n=41, 35, 31, 66	0 ± 0	36.3 ± 37.5	31.1 ± 13.7	33.9 ± 28.8
Cycle 3 Day 1: Cmax; n=37, 36, 31, 67	0 ± 0	77244.4 ± 36242.2	116687.1 ± 48446.8	95494 ± 46433.2
Cycle 4 Day 1: Trough; n=41, 35, 29, 64	0 ± 0	23.6 ± 6.2	38.6 ± 33.5	30.4 ± 24
Cycle 4 Day 1: Cmax; n=41, 37, 29, 66	0 ± 0	77613.5 ± 25373.7	109062.1 ± 35939.9	91431.8 ± 34064.1
Cycle 5 Day 1: Trough; n=36, 28, 25, 53	0 ± 0	26.1 ± 11.1	36.6 ± 26.2	31.1 ± 20.2
Cycle 5 Day 1: Cmax; n=36, 29, 26, 55	0.6 ± 3.8	72751.7 ± 24798.4	118319.2 ± 62796.8	94292.7 ± 51688.2
Cycle 6 Day 1: Trough; n=30, 24, 17, 41	0 ± 0	26.7 ± 13.1	38.4 ± 34	31.5 ± 24.4
Cycle 6 Day 1: Cmax; n=29, 23, 17, 40	0 ± 0	76474.7 ± 46557	125144.7 ± 63888.3	97159.5 ± 59084.5
EOT: Trough; n=34, 31, 31, 62	2.4 ± 13.9	25.2 ± 11.1	29.4 ± 24	27.3 ± 18.7

Notes
[28] - n=subjects with assessment at given time point
[29] - n=subjects with assessment at given time point
[30] - n=subjects with assessment at given time point
[31] - n=subjects with assessment at given time point

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose of study drug to 30 days after last dose of study drug (safety reporting period ranged from approximately 30 days to 850 days).

Adverse event reporting additional description

Events reported are treatment-emergent adverse events, defined as events which have a start date on or after the date of first study treatment administration and not more than 30 days after the date of the last study treatment administration.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

Placebo + Gem/Cis

Reporting group description

Participants received 3 loading doses of placebo within a 9-day period. Following the loading dose period, participants received weekly placebo infusions (IV) on Days 1, 8 and 15 of each 21-day cycle. Participants received chemotherapy consisting of up to 6 cycles of gemcitabine (1000 mg/m^2 IV on Days 1 and 8) and cisplatin (70 mg/m^2 IV on Day 1).

Reporting group title

OGX-427 600 mg + Gem/Cis

Reporting group description

Participants received 3 loading doses of 600 mg OGX-427 within a 9-day period. Following the loading dose period, participants received weekly OGX-427 infusions (600 mg IV) on Days 1, 8 and 15 of each 21-day cycle. Participants received chemotherapy consisting of up to 6 cycles of gemcitabine (1000 mg/m^2 IV on Days 1 and 8) and cisplatin (70 mg/m^2 IV on Day 1).

Reporting group title

OGX-427 1000 mg + Gem/Cis

Reporting group description

Participants received 3 loading doses of 600 mg OGX-427 within a 9-day period. Following the loading dose period, participants received weekly OGX-427 infusions (1000 mg IV) on Days 1, 8 and 15 of each 21-day cycle. Participants received chemotherapy consisting of up to 6 cycles of gemcitabine (1000 mg/m^2 IV on Days 1 and 8) and cisplatin (70 mg/m^2 IV on Day 1).

Reporting group title

Total OGX-427 + Gem/Cis

Reporting group description

Participants received 3 loading doses of 600 mg OGX-427 within a 9-day period. Following the loading dose period, participants received weekly OGX-427 infusions (600 mg or 1000 mg IV) on Days 1, 8 and 15 of each 21-day cycle. Participants received chemotherapy consisting of up to 6 cycles of gemcitabine (1000 mg/m^2 IV on Days 1 and 8) and cisplatin (70 mg/m^2 IV on Day 1).

Serious adverse events	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Total subjects affected by serious adverse events
subjects affected / exposed	26 / 61 (42.62%)	31 / 58 (53.45%)	37 / 60 (61.67%)	68 / 118 (57.63%)
number of deaths (all causes)	41	34	37	71
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour invasion
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tumour pain
subjects affected / exposed	2 / 61 (3.28%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 61 (1.64%)	3 / 58 (5.17%)	1 / 60 (1.67%)	4 / 118 (3.39%)
occurrences causally related to treatment / all	2 / 2	2 / 3	0 / 1	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	1 / 61 (1.64%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	2 / 60 (3.33%)	3 / 118 (2.54%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	1 / 60 (1.67%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 1	1 / 2
Asthenia
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Device occlusion
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthermia
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multi-organ failure
subjects affected / exposed	1 / 61 (1.64%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
Pain
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Epididymitis
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic pain
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	2 / 61 (3.28%)	3 / 58 (5.17%)	3 / 60 (5.00%)	6 / 118 (5.08%)
occurrences causally related to treatment / all	0 / 3	2 / 3	1 / 3	3 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	3 / 61 (4.92%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Delirium
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	2 / 60 (3.33%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Hip fracture
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 61 (1.64%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Chronic inflammatory demyelinating polyradiculoneuropathy
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Embolic cerebral infarction
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic encephalopathy
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hemiparesis
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	2 / 61 (3.28%)	3 / 58 (5.17%)	4 / 60 (6.67%)	7 / 118 (5.93%)
occurrences causally related to treatment / all	0 / 3	1 / 3	1 / 4	2 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 61 (1.64%)	2 / 58 (3.45%)	2 / 60 (3.33%)	4 / 118 (3.39%)
occurrences causally related to treatment / all	0 / 2	0 / 2	1 / 2	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	2 / 60 (3.33%)	3 / 118 (2.54%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 2	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	2 / 60 (3.33%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 61 (1.64%)	4 / 58 (6.90%)	1 / 60 (1.67%)	5 / 118 (4.24%)
occurrences causally related to treatment / all	0 / 1	0 / 4	1 / 1	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	3 / 60 (5.00%)	3 / 118 (2.54%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 61 (3.28%)	1 / 58 (1.72%)	2 / 60 (3.33%)	3 / 118 (2.54%)
occurrences causally related to treatment / all	0 / 2	0 / 1	2 / 3	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	3 / 61 (4.92%)	1 / 58 (1.72%)	1 / 60 (1.67%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	1 / 3	1 / 1	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 61 (1.64%)	1 / 58 (1.72%)	1 / 60 (1.67%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	1 / 1	0 / 1	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Ascites
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colonic pseudo-obstruction
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ileitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumatosis intestinalis
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct obstruction
subjects affected / exposed	0 / 61 (0.00%)	2 / 58 (3.45%)	0 / 60 (0.00%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperbilirubinaemia
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	3 / 60 (5.00%)	4 / 118 (3.39%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 3	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	1 / 60 (1.67%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure acute
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	1 / 60 (1.67%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Hydronephrosis
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	1 / 61 (1.64%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Bone pain
subjects affected / exposed	1 / 61 (1.64%)	1 / 58 (1.72%)	2 / 60 (3.33%)	3 / 118 (2.54%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteolysis
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Urinary tract infection
subjects affected / exposed	2 / 61 (3.28%)	1 / 58 (1.72%)	8 / 60 (13.33%)	9 / 118 (7.63%)
occurrences causally related to treatment / all	0 / 2	0 / 1	1 / 12	1 / 13
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 61 (1.64%)	2 / 58 (3.45%)	2 / 60 (3.33%)	4 / 118 (3.39%)
occurrences causally related to treatment / all	0 / 1	1 / 2	1 / 2	2 / 4
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 61 (1.64%)	3 / 58 (5.17%)	0 / 60 (0.00%)	3 / 118 (2.54%)
occurrences causally related to treatment / all	0 / 1	1 / 3	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	1 / 60 (1.67%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	3 / 3	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis salmonella
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 61 (4.92%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	1 / 4	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract abscess
subjects affected / exposed	0 / 61 (0.00%)	1 / 58 (1.72%)	0 / 60 (0.00%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium colitis
subjects affected / exposed	1 / 61 (1.64%)	0 / 58 (0.00%)	0 / 60 (0.00%)	0 / 118 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyponatraemia
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	3 / 60 (5.00%)	3 / 118 (2.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 3	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	1 / 61 (1.64%)	1 / 58 (1.72%)	1 / 60 (1.67%)	2 / 118 (1.69%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 61 (0.00%)	0 / 58 (0.00%)	1 / 60 (1.67%)	1 / 118 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo + Gem/Cis	OGX-427 600 mg + Gem/Cis	OGX-427 1000 mg + Gem/Cis	Total OGX-427 + Gem/Cis
Total subjects affected by non serious adverse events
subjects affected / exposed	61 / 61 (100.00%)	57 / 58 (98.28%)	59 / 60 (98.33%)	116 / 118 (98.31%)
Vascular disorders
Hypertension
subjects affected / exposed	10 / 61 (16.39%)	16 / 58 (27.59%)	12 / 60 (20.00%)	28 / 118 (23.73%)
occurrences all number	17	22	16	38
Flushing
subjects affected / exposed	2 / 61 (3.28%)	1 / 58 (1.72%)	5 / 60 (8.33%)	6 / 118 (5.08%)
occurrences all number	2	1	6	7
Thrombophlebitis
subjects affected / exposed	0 / 61 (0.00%)	4 / 58 (6.90%)	2 / 60 (3.33%)	6 / 118 (5.08%)
occurrences all number	0	4	2	6
General disorders and administration site conditions
Asthenia
subjects affected / exposed	28 / 61 (45.90%)	26 / 58 (44.83%)	25 / 60 (41.67%)	51 / 118 (43.22%)
occurrences all number	79	78	68	146
Pyrexia
subjects affected / exposed	10 / 61 (16.39%)	18 / 58 (31.03%)	22 / 60 (36.67%)	40 / 118 (33.90%)
occurrences all number	14	38	33	71
Fatigue
subjects affected / exposed	20 / 61 (32.79%)	18 / 58 (31.03%)	20 / 60 (33.33%)	38 / 118 (32.20%)
occurrences all number	40	42	36	78
Oedema peripheral
subjects affected / exposed	11 / 61 (18.03%)	19 / 58 (32.76%)	18 / 60 (30.00%)	37 / 118 (31.36%)
occurrences all number	16	21	25	46
Chills
subjects affected / exposed	2 / 61 (3.28%)	9 / 58 (15.52%)	14 / 60 (23.33%)	23 / 118 (19.49%)
occurrences all number	3	15	19	34
Chest pain
subjects affected / exposed	3 / 61 (4.92%)	4 / 58 (6.90%)	7 / 60 (11.67%)	11 / 118 (9.32%)
occurrences all number	3	5	9	14
Pain
subjects affected / exposed	3 / 61 (4.92%)	3 / 58 (5.17%)	3 / 60 (5.00%)	6 / 118 (5.08%)
occurrences all number	3	5	3	8
Reproductive system and breast disorders
Pelvic pain
subjects affected / exposed	0 / 61 (0.00%)	3 / 58 (5.17%)	5 / 60 (8.33%)	8 / 118 (6.78%)
occurrences all number	0	4	6	10
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	10 / 61 (16.39%)	13 / 58 (22.41%)	11 / 60 (18.33%)	24 / 118 (20.34%)
occurrences all number	12	15	12	27
Dyspnoea
subjects affected / exposed	12 / 61 (19.67%)	12 / 58 (20.69%)	12 / 60 (20.00%)	24 / 118 (20.34%)
occurrences all number	15	14	16	30
Pulmonary embolism
subjects affected / exposed	7 / 61 (11.48%)	5 / 58 (8.62%)	3 / 60 (5.00%)	8 / 118 (6.78%)
occurrences all number	7	6	3	9
Epistaxis
subjects affected / exposed	6 / 61 (9.84%)	3 / 58 (5.17%)	4 / 60 (6.67%)	7 / 118 (5.93%)
occurrences all number	9	3	4	7
Psychiatric disorders
Insomnia
subjects affected / exposed	8 / 61 (13.11%)	12 / 58 (20.69%)	7 / 60 (11.67%)	19 / 118 (16.10%)
occurrences all number	9	20	9	29
Anxiety
subjects affected / exposed	3 / 61 (4.92%)	3 / 58 (5.17%)	6 / 60 (10.00%)	9 / 118 (7.63%)
occurrences all number	3	4	7	11
Depression
subjects affected / exposed	4 / 61 (6.56%)	2 / 58 (3.45%)	5 / 60 (8.33%)	7 / 118 (5.93%)
occurrences all number	4	2	5	7
Investigations
Weight decreased
subjects affected / exposed	6 / 61 (9.84%)	4 / 58 (6.90%)	10 / 60 (16.67%)	14 / 118 (11.86%)
occurrences all number	7	4	12	16
Nervous system disorders
Dysgeusia
subjects affected / exposed	10 / 61 (16.39%)	10 / 58 (17.24%)	15 / 60 (25.00%)	25 / 118 (21.19%)
occurrences all number	11	15	16	31
Neuropathy peripheral
subjects affected / exposed	6 / 61 (9.84%)	11 / 58 (18.97%)	14 / 60 (23.33%)	25 / 118 (21.19%)
occurrences all number	6	14	23	37
Paraesthesia
subjects affected / exposed	7 / 61 (11.48%)	10 / 58 (17.24%)	8 / 60 (13.33%)	18 / 118 (15.25%)
occurrences all number	8	14	14	28
Headache
subjects affected / exposed	4 / 61 (6.56%)	9 / 58 (15.52%)	7 / 60 (11.67%)	16 / 118 (13.56%)
occurrences all number	5	13	8	21
Dizziness
subjects affected / exposed	5 / 61 (8.20%)	10 / 58 (17.24%)	5 / 60 (8.33%)	15 / 118 (12.71%)
occurrences all number	7	12	9	21
Peripheral sensory neuropathy
subjects affected / exposed	3 / 61 (4.92%)	4 / 58 (6.90%)	2 / 60 (3.33%)	6 / 118 (5.08%)
occurrences all number	4	5	2	7
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	33 / 61 (54.10%)	29 / 58 (50.00%)	31 / 60 (51.67%)	60 / 118 (50.85%)
occurrences all number	92	81	75	156
Anaemia
subjects affected / exposed	27 / 61 (44.26%)	25 / 58 (43.10%)	32 / 60 (53.33%)	57 / 118 (48.31%)
occurrences all number	64	59	95	154
Thrombocytopenia
subjects affected / exposed	21 / 61 (34.43%)	25 / 58 (43.10%)	24 / 60 (40.00%)	49 / 118 (41.53%)
occurrences all number	51	82	65	147
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	6 / 61 (9.84%)	5 / 58 (8.62%)	6 / 60 (10.00%)	11 / 118 (9.32%)
occurrences all number	7	6	6	12
Gastrointestinal disorders
Nausea
subjects affected / exposed	40 / 61 (65.57%)	31 / 58 (53.45%)	37 / 60 (61.67%)	68 / 118 (57.63%)
occurrences all number	88	74	70	144
Constipation
subjects affected / exposed	22 / 61 (36.07%)	25 / 58 (43.10%)	23 / 60 (38.33%)	48 / 118 (40.68%)
occurrences all number	31	33	38	71
Vomiting
subjects affected / exposed	25 / 61 (40.98%)	20 / 58 (34.48%)	19 / 60 (31.67%)	39 / 118 (33.05%)
occurrences all number	42	34	36	70
Diarrhoea
subjects affected / exposed	21 / 61 (34.43%)	16 / 58 (27.59%)	22 / 60 (36.67%)	38 / 118 (32.20%)
occurrences all number	24	32	33	65
Abdominal pain
subjects affected / exposed	8 / 61 (13.11%)	12 / 58 (20.69%)	13 / 60 (21.67%)	25 / 118 (21.19%)
occurrences all number	11	16	14	30
Dyspepsia
subjects affected / exposed	4 / 61 (6.56%)	8 / 58 (13.79%)	8 / 60 (13.33%)	16 / 118 (13.56%)
occurrences all number	5	10	8	18
Abdominal pain upper
subjects affected / exposed	3 / 61 (4.92%)	5 / 58 (8.62%)	6 / 60 (10.00%)	11 / 118 (9.32%)
occurrences all number	4	5	12	17
Abdominal distension
subjects affected / exposed	3 / 61 (4.92%)	5 / 58 (8.62%)	4 / 60 (6.67%)	9 / 118 (7.63%)
occurrences all number	4	5	5	10
Stomatitis
subjects affected / exposed	3 / 61 (4.92%)	4 / 58 (6.90%)	4 / 60 (6.67%)	8 / 118 (6.78%)
occurrences all number	3	4	5	9
Abdominal pain lower
subjects affected / exposed	6 / 61 (9.84%)	3 / 58 (5.17%)	3 / 60 (5.00%)	6 / 118 (5.08%)
occurrences all number	8	4	4	8
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	6 / 61 (9.84%)	7 / 58 (12.07%)	11 / 60 (18.33%)	18 / 118 (15.25%)
occurrences all number	9	8	11	19
Rash
subjects affected / exposed	5 / 61 (8.20%)	10 / 58 (17.24%)	8 / 60 (13.33%)	18 / 118 (15.25%)
occurrences all number	6	14	14	28
Pruritus
subjects affected / exposed	5 / 61 (8.20%)	8 / 58 (13.79%)	8 / 60 (13.33%)	16 / 118 (13.56%)
occurrences all number	5	9	9	18
Erythema
subjects affected / exposed	4 / 61 (6.56%)	3 / 58 (5.17%)	4 / 60 (6.67%)	7 / 118 (5.93%)
occurrences all number	4	4	4	8
Renal and urinary disorders
Renal impairment
subjects affected / exposed	21 / 61 (34.43%)	24 / 58 (41.38%)	28 / 60 (46.67%)	52 / 118 (44.07%)
occurrences all number	69	71	72	143
Haematuria
subjects affected / exposed	7 / 61 (11.48%)	6 / 58 (10.34%)	16 / 60 (26.67%)	22 / 118 (18.64%)
occurrences all number	15	8	25	33
Dysuria
subjects affected / exposed	2 / 61 (3.28%)	4 / 58 (6.90%)	6 / 60 (10.00%)	10 / 118 (8.47%)
occurrences all number	4	8	10	18
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	15 / 61 (24.59%)	13 / 58 (22.41%)	23 / 60 (38.33%)	36 / 118 (30.51%)
occurrences all number	25	16	68	84
Pain in extremity
subjects affected / exposed	8 / 61 (13.11%)	11 / 58 (18.97%)	9 / 60 (15.00%)	20 / 118 (16.95%)
occurrences all number	11	11	12	23
Muscle spasms
subjects affected / exposed	1 / 61 (1.64%)	6 / 58 (10.34%)	8 / 60 (13.33%)	14 / 118 (11.86%)
occurrences all number	1	9	12	21
Arthralgia
subjects affected / exposed	5 / 61 (8.20%)	4 / 58 (6.90%)	9 / 60 (15.00%)	13 / 118 (11.02%)
occurrences all number	10	6	10	16
Flank pain
subjects affected / exposed	3 / 61 (4.92%)	2 / 58 (3.45%)	6 / 60 (10.00%)	8 / 118 (6.78%)
occurrences all number	5	2	9	11
Muscular weakness
subjects affected / exposed	3 / 61 (4.92%)	4 / 58 (6.90%)	3 / 60 (5.00%)	7 / 118 (5.93%)
occurrences all number	3	5	6	11
Musculoskeletal pain
subjects affected / exposed	2 / 61 (3.28%)	4 / 58 (6.90%)	3 / 60 (5.00%)	7 / 118 (5.93%)
occurrences all number	2	6	4	10
Bone pain
subjects affected / exposed	3 / 61 (4.92%)	2 / 58 (3.45%)	4 / 60 (6.67%)	6 / 118 (5.08%)
occurrences all number	4	4	7	11
Infections and infestations
Urinary tract infection
subjects affected / exposed	18 / 61 (29.51%)	15 / 58 (25.86%)	16 / 60 (26.67%)	31 / 118 (26.27%)
occurrences all number	34	19	22	41
Upper respiratory tract infection
subjects affected / exposed	7 / 61 (11.48%)	7 / 58 (12.07%)	2 / 60 (3.33%)	9 / 118 (7.63%)
occurrences all number	7	9	2	11
Bronchitis
subjects affected / exposed	3 / 61 (4.92%)	4 / 58 (6.90%)	3 / 60 (5.00%)	7 / 118 (5.93%)
occurrences all number	4	5	3	8
Respiratory tract infection
subjects affected / exposed	5 / 61 (8.20%)	1 / 58 (1.72%)	5 / 60 (8.33%)	6 / 118 (5.08%)
occurrences all number	5	1	6	7
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	19 / 61 (31.15%)	18 / 58 (31.03%)	18 / 60 (30.00%)	36 / 118 (30.51%)
occurrences all number	28	26	29	55
Hypomagnesaemia
subjects affected / exposed	10 / 61 (16.39%)	9 / 58 (15.52%)	10 / 60 (16.67%)	19 / 118 (16.10%)
occurrences all number	23	18	22	40
Hypokalaemia
subjects affected / exposed	8 / 61 (13.11%)	8 / 58 (13.79%)	6 / 60 (10.00%)	14 / 118 (11.86%)
occurrences all number	13	16	9	25
Hyponatraemia
subjects affected / exposed	4 / 61 (6.56%)	6 / 58 (10.34%)	8 / 60 (13.33%)	14 / 118 (11.86%)
occurrences all number	6	6	18	24
Hyperglycaemia
subjects affected / exposed	2 / 61 (3.28%)	7 / 58 (12.07%)	3 / 60 (5.00%)	10 / 118 (8.47%)
occurrences all number	2	21	5	26
Hyperuricaemia
subjects affected / exposed	4 / 61 (6.56%)	5 / 58 (8.62%)	2 / 60 (3.33%)	7 / 118 (5.93%)
occurrences all number	5	7	2	9
Hypophosphataemia
subjects affected / exposed	1 / 61 (1.64%)	4 / 58 (6.90%)	2 / 60 (3.33%)	6 / 118 (5.08%)
occurrences all number	1	6	3	9

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Randomized, Double-Blind Phase 2 Study Comparing Gemcitabine and Cisplatin in Combination with OGX-427 or Placebo in Patients with Advanced Transitional Cell Carcinoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall Survival (OS)

Primary: Overall Survival (OS)

Secondary: Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs (SAEs), and Grade 3 or Higher AEs

Secondary: Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs (SAEs), and Grade 3 or Higher AEs

Secondary: Number of Participants With at ≥ 1 Hematology Abnormality and ≥ 1 Grade 3 or Higher Hematology Abnormality

Secondary: Number of Participants With at ≥ 1 Hematology Abnormality and ≥ 1 Grade 3 or Higher Hematology Abnormality

Secondary: Number of Participants With ≥ 1 Serum Chemistry Laboratory Abnormality and ≥ 1 Grade 3 or Higher Serum Chemistry Laboratory Abnormality

Secondary: Number of Participants With ≥ 1 Serum Chemistry Laboratory Abnormality and ≥ 1 Grade 3 or Higher Serum Chemistry Laboratory Abnormality

Secondary: Number of Participants With ≥ 1 Urinalysis Abnormality

Secondary: Number of Participants With ≥ 1 Urinalysis Abnormality

Secondary: Confirmed Best Objective Tumor Response

Secondary: Confirmed Best Objective Tumor Response

Secondary: Overall Response Rate (ORR) and Disease Control Rate

Secondary: Overall Response Rate (ORR) and Disease Control Rate

Secondary: Duration of ORR

Secondary: Duration of ORR

Secondary: Progression-free Survival (PFS)

Secondary: Progression-free Survival (PFS)

Secondary: Change From Baseline in Serum Hsp27 levels by End of Treatment

Secondary: Change From Baseline in Serum Hsp27 levels by End of Treatment

Secondary: Change From Baseline in Serum Clusterin Levels by End of Treatment

Secondary: Change From Baseline in Serum Clusterin Levels by End of Treatment

Secondary: Baseline to Last Post-baseline Shift in Circulating Tumor Cell (CTC) Count

Secondary: Baseline to Last Post-baseline Shift in Circulating Tumor Cell (CTC) Count

Secondary: Baseline to Last Post-baseline Change in CTC Count

Secondary: Baseline to Last Post-baseline Change in CTC Count

Secondary: Serum OGX-427 Maximum Plasma Concentration (Cmax) and Trough Levels

Secondary: Serum OGX-427 Maximum Plasma Concentration (Cmax) and Trough Levels

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Randomized, Double-Blind Phase 2 Study Comparing Gemcitabine and Cisplatin in Combination with OGX-427 or Placebo in Patients with Advanced Transitional Cell Carcinoma