Study of Enzastaurin Versus Placebo With Pemetrexed for P... | NCT00530621

ID	Type	Description	Link
H6Q-MC-JCBT	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Pemetrexed + Enzastaurin	Experimental		Drug: enzastaurin Drug: pemetrexed
Pemetrexed + Placebo	Placebo Comparator		Drug: placebo Drug: pemetrexed

Name	Type	Description	Arm Group Labels	Other Names
enzastaurin	Drug	1125 milligrams (mg) loading dose then 500 mg, oral, daily Cycle 1 (28 days), subsequent cycles 21 days, until disease progression	Pemetrexed + Enzastaurin

Measure	Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time from date of randomization to the first documented observation of disease progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death at the data inclusion cut-off date.	Baseline to measured progressive disease up to 9.92 months

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the date the participant was last known to be alive.	Baseline to date of death from any cause up to 12.32 months

Measure	Description	Time Frame
Number of Participants Who Died During the Study Treatment	Reported are the deaths due to study disease and adverse events (AEs) that occurred while on study treatment.	Baseline through study completion [up to 16 Cycles (21-day cycles, except Cycle 1 [28 days])]
Number of Participants Who Died During the 30 Days After Treatment Discontinuation

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Fayetteville	Arkansas	72703

ID	Title	Description
FG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-Free Survival (PFS)

PFS was defined as the time from date of randomization to the first documented observation of disease progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death at the data inclusion cut-off date.

All randomized participants. Twenty five (25) participants in Pemetrexed + Enzastaurin group and twenty three (23) participants in Pemetrexed + Placebo group were censored for analysis.

Posted

Median

95% Confidence Interval

months

Baseline to measured progressive disease up to 9.92 months

ID	Title	Description
OG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
OG001	Pemetrexed + Placebo	Placebo loading dose [total 9 tablets (3 tablets administered orally 3 times a day)] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

Units	Counts
Participants	OG00080 OG00180

Title

Denominators

Categories

Title	Measurements
	OG0002.96(1.87 to 3.58) OG0013.02(1.74 to 3.98)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.544	P-value was stratified by Eastern Cooperative Oncology Group (ECOG) performance status and time since last chemotherapy.	Hazard Ratio (HR)	1.13				95	0.77	1.65					Superiority or Other (legacy)

Secondary

Overall Survival (OS)

OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the date the participant was last known to be alive.

All randomized participants. Fifty three (53) participants in Pemetrexed + Enzastaurin group and forty five (45) participants in Pemetrexed + Placebo group were censored for analysis.

Posted

Median

95% Confidence Interval

months

Baseline to date of death from any cause up to 12.32 months

ID	Title	Description
OG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
OG001	Pemetrexed + Placebo	Placebo loading dose [total 9 tablets (3 tablets administered orally 3 times a day)] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

Secondary

Time-to-Worsening (TW) in Lung Cancer Symptom Scale (LCSS) - Health Related Quality of Life (HRQoL) Subscale

LCSS is a participant rated lung cancer instrument which consisted of 6 disease related symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 quality of life (QoL) items (activity status, symptomatic distress, and overall QoL). TW in LCSS-HRQoL was measured from the date of enrollment to the first date of a 15 millimeters (mm) worsening in the 9th LCSS item on QoL. LCSS-HRQoL was measured on the 100-mm visual analogue scale (VAS) with the scores ranging from 0 (best response and very high HRQoL) to 100-mm (worse response and very low HRQoL). TW-HRQoL was censored at the date of the participant's last LCSS assessment for participant without a 15-mm increase on the 100-mm VAS.

Randomized participants who had at least 1 baseline and 1 postbaseline LCSS assessment for HRQoL. Thirty (30) participants in Pemetrexed + Enzastaurin group and forty (40) participants in Pemetrexed + Placebo group were censored for the analysis.

Posted

Median

95% Confidence Interval

months

Baseline to disease worsening up to 10.58 months

ID	Title	Description
OG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

Secondary

Duration of Disease Control (DDC)

DDC was defined as the time from randomization to the first documented observation of disease progression or death from any cause and was limited to the participants with a best tumor response of complete response (CR), partial response (PR), or stable disease (SD). Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. SD was defined as small changes that did not meet the above criteria. DDC was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death.

Randomized participants who received at least 1 dose of study drug and had a best tumor response of CR, PR, or SD. Fourteen (14) participants in Pemetrexed + Enzastaurin group and seventeen (17) participants in Pemetrexed + Placebo group were censored for analysis.

Posted

Median

95% Confidence Interval

months

Baseline to measured progressive disease up to 9.92 months

ID	Title	Description
OG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

Secondary

Percentage of Participants With Complete Response or Partial Response (Tumor Response Rate)

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Participants with a best response of complete response (CR) or partial response (PR) were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants was calculated as the total number of participants affected divided by the number of participants analyzed then multiplied by 100.

Randomized participants who received at least 1 dose of study drug and had responses evaluated for CR or PR.

Posted

Number

percentage of participants

Baseline to measured progressive disease up to 9.92 months

ID	Title	Description
OG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets; three (125-mg) tablets administered orally 3 times a day] on Day 1 followed by total dose of 500 mg enzastaurin [two (125-mg) tablets administered orally 2 times a day] on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin [two (125-mg) tablets administered orally 2 times a day] on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

Secondary

Tumor Biomarkers

Protein expression was measured using an Immunohistochemistry (IHC) assay from the tumor tissue samples. IHC histo-scores (H-scores) were determined separately for each of the 3 biomarkers: folate receptor alpha (FR alpha) in cytoplasm and apical membrane, thymidylate synthase (TS) in cytoplasm and nucleus, and thyroid transcription factor-1 (TTF1) in the nucleus. Tumor tissue samples were to be scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining. IHC H-score was calculated using the formula: 1 * (percentage of cells stained 1+) + 2 * (percentage of cells stained 2+) + 3 * (percentage of cells stained 3+), giving a minimum score of 0 to a maximum score of 300. The maximum score indicates the strongest expression.

Randomized participants who had at least 1 biomarker expression value measured at baseline.

Posted

Mean

Standard Deviation

H-scores

Tumor samples collected at baseline

ID	Title	Description
OG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

Other Pre-specified

Number of Participants Who Died During the Study Treatment

Reported are the deaths due to study disease and adverse events (AEs) that occurred while on study treatment.

All randomized participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Baseline through study completion [up to 16 Cycles (21-day cycles, except Cycle 1 [28 days])]

ID	Title	Description
OG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
OG001	Pemetrexed + Placebo	Placebo loading dose [total 9 tablets (3 tablets administered orally 3 times a day)] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.

Other Pre-specified

Number of Participants Who Died During the 30 Days After Treatment Discontinuation

Reported are the deaths due to study disease and adverse events (AEs) that occurred during the 30 days after treatment discontinuation.

All randomized participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

End of study treatment [16 Cycles (21-day cycles, except Cycle 1 [28 days])] through 30 days after treatment discontinuation

ID	Title	Description
OG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
OG001	Pemetrexed + Placebo	Placebo loading dose [total 9 tablets (3 tablets administered orally 3 times a day)] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met. .

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0013 events3 affected80 at risk
Anaemia of malignant disease	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Febrile neutropenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0003 events3 affected79 at risk EG0010 events0 affected80 at risk
Leukopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected80 at risk
Neutropenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0012 events2 affected80 at risk
Pancytopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Thrombocytopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0011 events1 affected80 at risk
Atrial fibrillation	Cardiac disorders	16.0	Systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected80 at risk
Cardiac failure acute	Cardiac disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Palpitations	Cardiac disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Pericardial effusion	Cardiac disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Adrenal insufficiency	Endocrine disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Abdominal pain upper	Gastrointestinal disorders	16.0	Systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected80 at risk
Anal ulcer	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Diarrhoea	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0013 events3 affected80 at risk
Dysphagia	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Gastrointestinal perforation	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Haematochezia	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Nausea	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0013 events3 affected80 at risk
Oesophageal stenosis	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0012 events2 affected80 at risk
Oesophagitis	Gastrointestinal disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Subileus	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Vomiting	Gastrointestinal disorders	16.0	Systematic Assessment	EG0004 events4 affected79 at risk EG0013 events3 affected80 at risk
Asthenia	General disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Chest pain	General disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Disease progression	General disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Fatigue	General disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0012 events2 affected80 at risk
General physical health deterioration	General disorders	16.0	Systematic Assessment	EG0005 events5 affected79 at risk EG0011 events1 affected80 at risk
Mucosal inflammation	General disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Pyrexia	General disorders	16.0	Systematic Assessment	EG0003 events3 affected79 at risk EG0013 events2 affected80 at risk
Cholangitis	Hepatobiliary disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Febrile infection	Infections and infestations	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0011 events1 affected80 at risk
Listeriosis	Infections and infestations	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Lower respiratory tract infection	Infections and infestations	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Neutropenic sepsis	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0012 events2 affected80 at risk
Pneumonia	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0016 events4 affected80 at risk
Staphylococcal infection	Infections and infestations	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Femur fracture	Injury, poisoning and procedural complications	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Subdural haematoma	Injury, poisoning and procedural complications	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Upper limb fracture	Injury, poisoning and procedural complications	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Blood creatinine increased	Investigations	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Dehydration	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0014 events4 affected80 at risk
Hypercalcaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Hypokalaemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Hyponatraemia	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Malnutrition	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Back pain	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0012 events2 affected80 at risk
Bone pain	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	16.0	Systematic Assessment	EG0002 events1 affected79 at risk EG0013 events1 affected80 at risk
Cerebrovascular accident	Nervous system disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0011 events1 affected80 at risk
Syncope	Nervous system disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Abnormal behaviour	Psychiatric disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Completed suicide	Psychiatric disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Renal failure	Renal and urinary disorders	16.0	Systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected80 at risk
Renal pain	Renal and urinary disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Bronchial fistula	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0003 events3 affected79 at risk EG0011 events1 affected80 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected80 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Mediastinal disorder	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk
Panniculitis	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected80 at risk
Rash	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0012 events2 affected80 at risk
Hypotension	Vascular disorders	16.0	Systematic Assessment	EG0000 events0 affected79 at risk EG0012 events2 affected80 at risk
Thrombosis	Vascular disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected80 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG00026 events23 affected79 at risk EG00122 events15 affected80 at risk
Leukopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0007 events4 affected79 at risk EG0018 events3 affected80 at risk
Lymphopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG0009 events5 affected79 at risk EG0017 events5 affected80 at risk
Neutropenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG00016 events15 affected79 at risk EG0019 events6 affected80 at risk
Thrombocytopenia	Blood and lymphatic system disorders	16.0	Systematic Assessment	EG00018 events11 affected79 at risk EG00114 events5 affected80 at risk
Vertigo	Ear and labyrinth disorders	16.0	Systematic Assessment	EG0007 events5 affected79 at risk EG0014 events4 affected80 at risk
Lacrimation increased	Eye disorders	16.0	Systematic Assessment	EG0007 events7 affected79 at risk EG0016 events6 affected80 at risk
Abdominal pain	Gastrointestinal disorders	16.0	Systematic Assessment	EG0001 events1 affected79 at risk EG00111 events8 affected80 at risk
Abdominal pain upper	Gastrointestinal disorders	16.0	Systematic Assessment	EG0006 events6 affected79 at risk EG0015 events4 affected80 at risk
Constipation	Gastrointestinal disorders	16.0	Systematic Assessment	EG00020 events19 affected79 at risk EG00119 events16 affected80 at risk
Diarrhoea	Gastrointestinal disorders	16.0	Systematic Assessment	EG00025 events17 affected79 at risk EG00113 events11 affected80 at risk
Dyspepsia	Gastrointestinal disorders	16.0	Systematic Assessment	EG0003 events3 affected79 at risk EG0016 events5 affected80 at risk
Nausea	Gastrointestinal disorders	16.0	Systematic Assessment	EG00052 events38 affected79 at risk EG00129 events20 affected80 at risk
Vomiting	Gastrointestinal disorders	16.0	Systematic Assessment	EG00025 events19 affected79 at risk EG00118 events14 affected80 at risk
Asthenia	General disorders	16.0	Systematic Assessment	EG00022 events19 affected79 at risk EG00126 events17 affected80 at risk
Chest pain	General disorders	16.0	Systematic Assessment	EG0009 events9 affected79 at risk EG00111 events11 affected80 at risk
Fatigue	General disorders	16.0	Systematic Assessment	EG00029 events23 affected79 at risk EG00127 events24 affected80 at risk
General physical health deterioration	General disorders	16.0	Systematic Assessment	EG0002 events2 affected79 at risk EG0015 events5 affected80 at risk
Mucosal inflammation	General disorders	16.0	Systematic Assessment	EG00013 events8 affected79 at risk EG0015 events5 affected80 at risk
Oedema	General disorders	16.0	Systematic Assessment	EG0005 events4 affected79 at risk EG0013 events3 affected80 at risk
Oedema peripheral	General disorders	16.0	Systematic Assessment	EG00013 events11 affected79 at risk EG0019 events8 affected80 at risk
Pyrexia	General disorders	16.0	Systematic Assessment	EG00028 events16 affected79 at risk EG00118 events14 affected80 at risk
Candidiasis	Infections and infestations	16.0	Systematic Assessment	EG0007 events7 affected79 at risk EG0011 events1 affected80 at risk
Alanine aminotransferase increased	Investigations	16.0	Systematic Assessment	EG0006 events6 affected79 at risk EG0015 events5 affected80 at risk
Aspartate aminotransferase increased	Investigations	16.0	Systematic Assessment	EG0005 events4 affected79 at risk EG0018 events5 affected80 at risk
Platelet count decreased	Investigations	16.0	Systematic Assessment	EG0004 events4 affected79 at risk EG0011 events1 affected80 at risk
Weight decreased	Investigations	16.0	Systematic Assessment	EG0009 events9 affected79 at risk EG0018 events8 affected80 at risk
Decreased appetite	Metabolism and nutrition disorders	16.0	Systematic Assessment	EG00037 events28 affected79 at risk EG00116 events15 affected80 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0003 events3 affected79 at risk EG0015 events4 affected80 at risk
Back pain	Musculoskeletal and connective tissue disorders	16.0	Systematic Assessment	EG0002 events2 affected79 at risk EG0018 events8 affected80 at risk
Dizziness	Nervous system disorders	16.0	Systematic Assessment	EG00013 events10 affected79 at risk EG0015 events5 affected80 at risk
Headache	Nervous system disorders	16.0	Systematic Assessment	EG0008 events7 affected79 at risk EG0013 events3 affected80 at risk
Neuropathy peripheral	Nervous system disorders	16.0	Systematic Assessment	EG0006 events5 affected79 at risk EG0013 events3 affected80 at risk
Anxiety	Psychiatric disorders	16.0	Systematic Assessment	EG0004 events4 affected79 at risk EG0012 events2 affected80 at risk
Confusional state	Psychiatric disorders	16.0	Systematic Assessment	EG0004 events4 affected79 at risk EG0010 events0 affected80 at risk
Depression	Psychiatric disorders	16.0	Systematic Assessment	EG0004 events4 affected79 at risk EG0013 events3 affected80 at risk
Insomnia	Psychiatric disorders	16.0	Systematic Assessment	EG0007 events7 affected79 at risk EG00113 events8 affected80 at risk
Chromaturia	Renal and urinary disorders	16.0	Systematic Assessment	EG0008 events8 affected79 at risk EG0011 events1 affected80 at risk
Cough	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG00016 events15 affected79 at risk EG00119 events16 affected80 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0003 events3 affected79 at risk EG0014 events4 affected80 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG00013 events13 affected79 at risk EG00116 events15 affected80 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0003 events2 affected79 at risk EG0014 events4 affected80 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0006 events6 affected79 at risk EG0012 events2 affected80 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	16.0	Systematic Assessment	EG0005 events5 affected79 at risk EG0012 events2 affected80 at risk
Night sweats	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0004 events4 affected79 at risk EG0013 events3 affected80 at risk
Pruritus	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG0003 events3 affected79 at risk EG00110 events8 affected80 at risk
Rash	Skin and subcutaneous tissue disorders	16.0	Systematic Assessment	EG00016 events13 affected79 at risk EG00115 events13 affected80 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000600	Amino Acids, Dicarboxylic

ID	Title	Description
BG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
BG001	Pemetrexed + Placebo	Placebo loading dose [total 9 tablets (3 tablets administered orally 3 times a day)] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pemetrexed + Enzastaurin	Enzastaurin 1125 milligrams (mg) loading dose [total 9 tablets (three 125-mg tablets administered orally 3 times a day)] on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 2 to 28, and pemetrexed 500 milligrams per square meter (mg/m^2) intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by total dose of 500 mg enzastaurin (two 125-mg tablets administered orally 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.			33	79	73	79
EG001	Pemetrexed + Placebo	Placebo loading dose [total 9 tablets (3 tablets administered orally 3 times a day)] on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 2 to 28, and pemetrexed 500 mg/m^2 intravenous injection on Day 8 in Cycle 1 (28-day cycle). Pemetrexed 500 mg/m^2 intravenous injection on Day 1 followed by 4 placebo tablets (2 tablets 2 times a day) on Days 1 to 21 in Cycle 2 and subsequent cycles (21-day cycle). Treatment was continued until evidence of disease progression, unacceptable toxicity, or any other discontinuation criteria were met.			30	80	75	80