Trial Outcomes & Findings for A Study of Enzastaurin and Erlotinib in Participants With Solid Tumors and Lung Cancer (NCT NCT00452413)
NCT ID: NCT00452413
Last Updated: 2021-05-13
Results Overview
The recommended Phase 2 daily dose level was to be either 1 dose level below that in which 2 of 6 participants experienced dose-limiting toxicities (DLTs) in Phase 1 or the full doses of both enzastaurin and erlotinib (Phase 1, Dose Level 2) in the event that no more than 1 DLT occurred at the highest dose level (Dose Level 2). DLTs were defined as any of the following events during Phase 1, Cycle 1 that were considered by the investigator to be attributable to enzastaurin or the combination of enzastaurin with erlotinib: Grade 4 hematologic events; Grade 3 or 4 nonhematologic events except toxicities explained by a coexisting condition such as glucose disturbances in a diabetic or electrolyte imbalances from diarrhea or vomiting, and toxicities of nausea, vomiting, diarrhea, or skin rash that were tolerable with appropriate treatment.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
65 participants
Primary outcome timeframe
Phase 1: Predose through end of Cycle 1 (28 days/cycle)
Results posted on
2021-05-13
Participant Flow
This study included 2 phases: Phase 1, a dose-escalation phase (employing a standard "3 + 3" design with dose escalation to Dose Level 2 based upon observed toxicity) and Phase 2, a dose-confirmation phase.
Participant milestones
| Measure |
Phase 1, Dose 1 (Enzastaurin 250 mg, Erlotinib 150 mg)
Enzastaurin: 500 milligram (mg) enzastaurin loading dose \[250 mg twice daily (BID)\] administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 250 mg dose administered once daily (QD).
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose \[375 mg 3 times daily (TID)\] administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg total daily dose administered orally using either a BID or QD schedule.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
12
|
49
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
4
|
12
|
49
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
4
|
12
|
49
|
Reasons for withdrawal
| Measure |
Phase 1, Dose 1 (Enzastaurin 250 mg, Erlotinib 150 mg)
Enzastaurin: 500 milligram (mg) enzastaurin loading dose \[250 mg twice daily (BID)\] administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 250 mg dose administered once daily (QD).
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose \[375 mg 3 times daily (TID)\] administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg total daily dose administered orally using either a BID or QD schedule.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|---|
|
Overall Study
Progressive Disease
|
4
|
11
|
30
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
4
|
|
Overall Study
Adverse Event
|
0
|
0
|
5
|
|
Overall Study
Physician Decision
|
0
|
0
|
4
|
|
Overall Study
Death due to study disease
|
0
|
0
|
2
|
|
Overall Study
Death due to adverse event (AE)
|
0
|
0
|
1
|
|
Overall Study
On treatment
|
0
|
0
|
3
|
Baseline Characteristics
A Study of Enzastaurin and Erlotinib in Participants With Solid Tumors and Lung Cancer
Baseline characteristics by cohort
| Measure |
Phase 1, Dose 1 (Enzastaurin 250 mg, Erlotinib 150 mg)
n=4 Participants
Enzastaurin: 500 mg enzastaurin loading dose (250 mg BID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 250 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=12 Participants
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=49 Participants
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg total daily dose administered orally using either a BID or QD schedule.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Total
n=65 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
74.0 years
FULL_RANGE 10.5 • n=5 Participants
|
62.5 years
FULL_RANGE 8.45 • n=7 Participants
|
67.0 years
FULL_RANGE 9.19 • n=5 Participants
|
66.0 years
FULL_RANGE NA • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
3 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
African
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
4 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
|
Stage of Disease at Initial Diagnosis
Stage IIIB
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Stage of Disease at Initial Diagnosis
Stage IV
|
4 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Phase 1: Predose through end of Cycle 1 (28 days/cycle)Population: Participants enrolled in Phase 1 who received at least 1 dose of study drug (either enzastaurin or erlotinib).
The recommended Phase 2 daily dose level was to be either 1 dose level below that in which 2 of 6 participants experienced dose-limiting toxicities (DLTs) in Phase 1 or the full doses of both enzastaurin and erlotinib (Phase 1, Dose Level 2) in the event that no more than 1 DLT occurred at the highest dose level (Dose Level 2). DLTs were defined as any of the following events during Phase 1, Cycle 1 that were considered by the investigator to be attributable to enzastaurin or the combination of enzastaurin with erlotinib: Grade 4 hematologic events; Grade 3 or 4 nonhematologic events except toxicities explained by a coexisting condition such as glucose disturbances in a diabetic or electrolyte imbalances from diarrhea or vomiting, and toxicities of nausea, vomiting, diarrhea, or skin rash that were tolerable with appropriate treatment.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=16 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Recommended Phase 2 Dose for Enzastaurin Plus Erlotinib Combination Therapy (Assess the Tolerated Dose of the Combination Erlotinib and Enzastaurin)
Erlotinib
|
150 milligrams per day (mg/day)
|
—
|
|
Recommended Phase 2 Dose for Enzastaurin Plus Erlotinib Combination Therapy (Assess the Tolerated Dose of the Combination Erlotinib and Enzastaurin)
Enzastaurin
|
500 milligrams per day (mg/day)
|
—
|
PRIMARY outcome
Timeframe: Phase 2: Baseline to measured PD (up to 20 months)Population: Participants enrolled in Phase 2 who received at least 1 dose of study drug (either enzastaurin or erlotinib). Eight participants were censored.
PFS was defined as the time from the date of study enrollment (baseline) to the first date of progressive disease (PD) (either objectively determined or clinical progression) or death from any cause. PD was defined by Response Evaluation Criteria in Solid Tumors \[RECIST, version (v) 1.0\] as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died as of the data cut-off date and who did not have PD, PFS was censored at the date of the last visit with adequate assessment. For participants who received subsequent anticancer therapy (after discontinuation from study treatment) prior to disease progression or death, PFS was censored at the date of last visit with adequate assessment prior to the initiation of post discontinuation anticancer therapy.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=41 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase 2: Progression-Free Survival (PFS) With the Enzastaurin Plus Erlotinib Combination Regimen
|
1.7 months
Interval 1.5 to
The measure of dispersion was a 1-sided confidence interval at the significance level of 0.10.
|
—
|
SECONDARY outcome
Timeframe: Phase 1: First dose through 30 days post last dose (up to 14 Cycles, 28 days/cycle)Population: Participants enrolled in Phase 1 who received at least 1 dose of study drug (either enzastaurin or erlotinib).
A TEAE is any untoward medical occurrence that either occurred or worsened any time after treatment baseline, which did not necessarily have a causal relationship with this treatment. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=4 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=12 Participants
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase I: Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) (Safety and AE Profile for Enzastaurin/Erlotinib Combination)
|
4 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Phase 1: Cycle 1, Day 22 [predose, 2 hours (h), 4 h, 6 h, 10 h postdose]Population: Participants enrolled in Phase 1 who received at least 1 dose of study drug (enzastaurin or erlotinib) and had adequate sample data to estimate CLss/F of erlotinib.
Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL obtained after an oral dose (apparent oral CL) is influenced by the fraction of the dose absorbed (F). Drug CL is a quantitative measure of the rate at which a drug substance is removed from the blood. Apparent oral CL of erlotinib over 10 hours at steady state (ss) on Day 22 was calculated.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=3 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=11 Participants
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase I: Pharmacokinetic (PK) Interactions Between Enzastaurin and Erlotinib: Apparent Oral Clearance of Erlotinib Under Steady State Conditions During Multiple Dosing (CLss/F)
|
6.07 Liters per hour (L/h)
Geometric Coefficient of Variation 19
|
5.75 Liters per hour (L/h)
Geometric Coefficient of Variation 45
|
SECONDARY outcome
Timeframe: Phase 1: Cycle 1, Day 22 (predose, 2 h, 4 h, 6 h, 8 h postdose)Population: Participants enrolled in Phase 1 who received at least 1 dose of study drug (enzastaurin or erlotinib) and had adequate sample data to estimate Cmax,ss of enzastaurin, its active metabolite and total analyte.
Maximum observed plasma concentration at steady state (Cmax,ss) of enzastaurin, its active metabolite (LSN326020) and total analyte were reported.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=3 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=12 Participants
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase I: PK Interactions Between Enzastaurin and Erlotinib: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Enzastaurin
|
618 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 709
|
1600 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 57
|
|
Phase I: PK Interactions Between Enzastaurin and Erlotinib: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
LSN326020
|
431 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 806
|
980 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 41
|
|
Phase I: PK Interactions Between Enzastaurin and Erlotinib: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Total Analyte
|
978 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 797
|
2620 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 44
|
SECONDARY outcome
Timeframe: Phase 1, Cycle 1, Day 22 (predose, 2 h, 4 h, 6 h, and 8 h postdose)Population: Participants enrolled in Phase 1 who received at least 1 dose of study drug (enzastaurin or erlotinib) and had adequate sample data to estimate AUC(Tau,ss) of enzastaurin, its active metabolite, and total analyte.
Area under the plasma concentration time curve AUC(Tau,ss) of enzastaurin, its active metabolite (LSN326020) and total analyte were reported.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=3 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=12 Participants
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase I: PK Interactions Between Enzastaurin and Erlotinib: Area Under the Plasma Concentration Time Curve at Steady State [AUC(Tau,ss)]
Enzastaurin
|
6590 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 412
|
18000 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 71
|
|
Phase I: PK Interactions Between Enzastaurin and Erlotinib: Area Under the Plasma Concentration Time Curve at Steady State [AUC(Tau,ss)]
LSN326020
|
7100 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 890
|
18000 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 44
|
|
Phase I: PK Interactions Between Enzastaurin and Erlotinib: Area Under the Plasma Concentration Time Curve at Steady State [AUC(Tau,ss)]
Total Analyte
|
14000 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 598
|
37100 nanomoles*hours per liter (nmol*h/L)
Geometric Coefficient of Variation 51
|
SECONDARY outcome
Timeframe: Phase 2: Baseline to date of death from any cause (up to 23 months)Population: Participants enrolled in Phase 2 who received at least 1 dose of study drug (either enzastaurin or erlotinib). Eighteen participants were censored.
OS was defined as the time from the date of study enrollment (baseline) to the date of death from any cause. For participants not known to have died as of the data cutoff date, OS was censored at the last contact date (last contact for participants in post discontinuation was equal to the last known alive date in mortality status).
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=31 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase 2: Overall Survival (OS)
|
8.3 months
Interval 5.3 to 14.3
|
—
|
SECONDARY outcome
Timeframe: Phase 2: Date of first response to date of PD (up to 18 months)Population: Participants enrolled in Phase 2 who received at least 1 dose of study drug (either enzastaurin or erlotinib) and had a CR or PR response. Two participants were censored.
Duration of response: time from first objective assessment of complete response (CR) or partial response (PR) to first observation of PD. Using RECIST v1.0 criteria, CR was the disappearance of all target lesions; PR was either a ≥30% decrease in sum of LD of target lesions or a complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesion; PD was a ≥20% increase in sum of LD of target lesions, taking as references the smallest sum LD recorded since treatment started or the appearance of ≥1 new lesion. For responding participants not known to have died and who did not have PD, duration of response was censored at date of the last visit with adequate assessment. For responding participants who received subsequent anticancer therapy (after discontinuation from study treatment) prior to PD, duration of response was censored at the date of last visit with adequate assessment prior to the initiation of post discontinuation anticancer therapy.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=3 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase 2: Duration of Response
|
8.7 months
Interval 7.5 to
The upper 95% confidence interval was not estimable because an insufficient number of participants reached the event at the final time point for assessment.
|
—
|
SECONDARY outcome
Timeframe: Phase 2: Baseline to date of PD (up to 18 months)Population: Participants enrolled in Phase 2 who received at least 1 dose of study drug (either enzastaurin or erlotinib).
Tumor response was defined using RECIST, v1.0 criteria. CR was the disappearance of all target lesions; PR was either a ≥30% decrease in sum of LD of target lesions or a complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesion. PD was a ≥20% increase in sum of LD of target lesions, taking as references the smallest sum LD recorded since treatment started or the appearance of ≥1 new lesion. Stable Disease (SD) was defined as small changes that did not meet the above criteria. Percentage of participants with tumor response=\[(number of participants with a CR, PR, SD, PD, and unknown response)/(total number of participants assessed)\]\*100.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=49 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase 2: Percentage of Participants With Tumor Response
CR
|
0 percentage of participants
Interval 0.0 to 7.3
|
—
|
|
Phase 2: Percentage of Participants With Tumor Response
SD
|
20.4 percentage of participants
Interval 10.2 to 34.3
|
—
|
|
Phase 2: Percentage of Participants With Tumor Response
PD
|
42.9 percentage of participants
Interval 28.8 to 57.8
|
—
|
|
Phase 2: Percentage of Participants With Tumor Response
PR
|
10.2 percentage of participants
Interval 3.4 to 22.2
|
—
|
|
Phase 2: Percentage of Participants With Tumor Response
Unknown
|
26.5 percentage of participants
Interval 14.9 to 41.1
|
—
|
SECONDARY outcome
Timeframe: Phase 2: Baseline through 30 days post last dose (up to 24 Cycles, 28 days/cycle)Population: Participants enrolled in Phase 2 who received at least 1 dose of study drug (either enzastaurin or erlotinib).
A TEAE is any untoward medical occurrence that either occurred or worsened any time after treatment baseline, which did not necessarily have a causal relationship with this treatment. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Phase 1, Dose 1 and 2 (Enzastaurin and Erlotinib)
n=49 Participants
Enzastaurin: Either 500 mg or 1125 mg enzastaurin loading dose administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, either 250 mg or 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD.
Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|
|
Phase 2: Number of Participants Who Experienced TEAEs (Safety and AE Profile)
|
48 participants
|
—
|
Adverse Events
Phase 1, Dose 1 (Enzastaurin 250 mg, Erlotinib 150 mg)
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Phase 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
Serious events: 18 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1, Dose 1 (Enzastaurin 250 mg, Erlotinib 150 mg)
n=4 participants at risk
Enzastaurin: 500 milligram (mg) enzastaurin loading dose \[250 mg twice daily (BID)\] administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 250 mg dose administered once daily (QD).
Erlotinib: 150 mg dose of erlotinib administered orally QD. Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=12 participants at risk
Enzastaurin: 1125 mg enzastaurin loading dose \[375 mg 3 times daily (TID)\] administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD. Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=49 participants at risk
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg total daily dose administered orally using either a BID or QD schedule.
Erlotinib: 150 mg dose of erlotinib administered orally QD. Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Cardiac disorders
Coronary artery occlusion
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Diplopia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Drug interaction
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
General disorders
Pyrexia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Paronychia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/4
|
0.00%
0/12
|
8.2%
4/49 • Number of events 4
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Injury, poisoning and procedural complications
Radiation pneumonitis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Ataxia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Bronchostenosis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
25.0%
1/4 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
25.0%
1/4 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Vascular disorders
Superior vena cava syndrome
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
Other adverse events
| Measure |
Phase 1, Dose 1 (Enzastaurin 250 mg, Erlotinib 150 mg)
n=4 participants at risk
Enzastaurin: 500 milligram (mg) enzastaurin loading dose \[250 mg twice daily (BID)\] administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 250 mg dose administered once daily (QD).
Erlotinib: 150 mg dose of erlotinib administered orally QD. Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 1, Dose 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=12 participants at risk
Enzastaurin: 1125 mg enzastaurin loading dose \[375 mg 3 times daily (TID)\] administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg dose administered QD.
Erlotinib: 150 mg dose of erlotinib administered orally QD. Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
Phase 2 (Enzastaurin 500 mg, Erlotinib 150 mg)
n=49 participants at risk
Enzastaurin: 1125 mg enzastaurin loading dose (375 mg TID) administered orally on Day 1 of a 28-day cycle. Day 2 through Day 28, 500 mg total daily dose administered orally using either a BID or QD schedule.
Erlotinib: 150 mg dose of erlotinib administered orally QD. Treatment continued until disease progression, unacceptable toxicity, or study withdrawal criteria were met.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/4
|
0.00%
0/12
|
14.3%
7/49 • Number of events 9
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Blood and lymphatic system disorders
Leukocytosis
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 2
|
0.00%
0/49
|
|
Blood and lymphatic system disorders
Nucleated red cells
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/4
|
0.00%
0/12
|
10.2%
5/49 • Number of events 5
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Cardiac disorders
Bundle branch block left
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Cardiac disorders
Extrasystoles
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Cardiac disorders
Palpitations
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Ear and labyrinth disorders
Otorrhoea
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 2
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Blepharitis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 5
|
|
Eye disorders
Diplopia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Dry eye
|
25.0%
1/4 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
8.2%
4/49 • Number of events 4
|
|
Eye disorders
Erythema of eyelid
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Eye irritation
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Eyelash thickening
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Eye disorders
Eyelid disorder
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Eye disorders
Eyelid ptosis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Growth of eyelashes
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Macular oedema
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Eye disorders
Periorbital oedema
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Eye disorders
Retinal haemorrhage
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Vision blurred
|
0.00%
0/4
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Eye disorders
Visual impairment
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/4
|
8.3%
1/12 • Number of events 2
|
0.00%
0/49
|
|
Gastrointestinal disorders
Abdominal distension
|
25.0%
1/4 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
4.1%
2/49 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain
|
50.0%
2/4 • Number of events 2
|
25.0%
3/12 • Number of events 3
|
4.1%
2/49 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
0.00%
0/49
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
6.1%
3/49 • Number of events 4
|
|
Gastrointestinal disorders
Anorectal discomfort
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Chapped lips
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 2
|
0.00%
0/49
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
16.3%
8/49 • Number of events 8
|
|
Gastrointestinal disorders
Diarrhoea
|
100.0%
4/4 • Number of events 4
|
91.7%
11/12 • Number of events 13
|
73.5%
36/49 • Number of events 54
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
4.1%
2/49 • Number of events 2
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 2
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Epigastric discomfort
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Faeces discoloured
|
25.0%
1/4 • Number of events 1
|
58.3%
7/12 • Number of events 8
|
6.1%
3/49 • Number of events 3
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4
|
66.7%
8/12 • Number of events 9
|
42.9%
21/49 • Number of events 23
|
|
Gastrointestinal disorders
Oral discomfort
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Gastrointestinal disorders
Oral mucosal discolouration
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Oral papule
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Gastrointestinal disorders
Post-tussive vomiting
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/4
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
|
Gastrointestinal disorders
Tongue ulceration
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Gastrointestinal disorders
Toothache
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4
|
41.7%
5/12 • Number of events 7
|
24.5%
12/49 • Number of events 12
|
|
General disorders
Asthenia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Chest discomfort
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
|
General disorders
Chills
|
0.00%
0/4
|
25.0%
3/12 • Number of events 3
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Early satiety
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
General disorders
Facial pain
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
General disorders
Fatigue
|
50.0%
2/4 • Number of events 2
|
75.0%
9/12 • Number of events 10
|
42.9%
21/49 • Number of events 26
|
|
General disorders
Feeling cold
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Feeling hot
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Feeling jittery
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Gait disturbance
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Influenza like illness
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Injection site bruising
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Local swelling
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Localised oedema
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
General disorders
Oedema
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
0.00%
0/49
|
|
General disorders
Oedema peripheral
|
0.00%
0/4
|
16.7%
2/12 • Number of events 3
|
6.1%
3/49 • Number of events 3
|
|
General disorders
Pain
|
0.00%
0/4
|
25.0%
3/12 • Number of events 3
|
4.1%
2/49 • Number of events 2
|
|
General disorders
Pyrexia
|
50.0%
2/4 • Number of events 3
|
8.3%
1/12 • Number of events 1
|
8.2%
4/49 • Number of events 4
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 6
|
|
Immune system disorders
Contrast media allergy
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Infections and infestations
Candida infection
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Infections and infestations
Cellulitis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Cystitis
|
25.0%
1/4 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Infection
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Infections and infestations
Influenza
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Nail infection
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Paronychia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 4
|
|
Infections and infestations
Pneumonia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Rash pustular
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Sepsis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Sinusitis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Tinea infection
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
10.2%
5/49 • Number of events 5
|
|
Infections and infestations
Vaginal abscess
|
0.00%
0/4
|
0.00%
0/9
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Viral infection
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/4
|
8.3%
1/12 • Number of events 2
|
0.00%
0/49
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Injury, poisoning and procedural complications
Sunburn
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/4
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
|
Investigations
Aspartate aminotransferase decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/4
|
0.00%
0/12
|
8.2%
4/49 • Number of events 4
|
|
Investigations
Band neutrophil count increased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Blood albumin decreased
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
4.1%
2/49 • Number of events 2
|
|
Investigations
Blood alkaline phosphatase
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
10.2%
5/49 • Number of events 5
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/4
|
0.00%
0/12
|
8.2%
4/49 • Number of events 6
|
|
Investigations
Blood chloride decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Blood cholesterol increased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Blood creatinine increased
|
0.00%
0/4
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
|
Investigations
Blood lactate dehydrogenase decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Blood lactic acid increased
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Investigations
Blood methaemoglobin present
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Blood urea increased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Blood urine present
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
C-reactive protein increased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Cardiac murmur
|
25.0%
1/4 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Investigations
Electrocardiogram abnormal
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Fibrin d dimer increased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Haematocrit decreased
|
0.00%
0/4
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/4
|
0.00%
0/12
|
8.2%
4/49 • Number of events 5
|
|
Investigations
Heart rate decreased
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Investigations
Mean cell haemoglobin decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Mean cell volume decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Monocyte count decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Neutrophil count increased
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Investigations
Neutrophil percentage decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Neutrophil percentage increased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 2
|
|
Investigations
Platelet count decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Platelet count increased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Prealbumin decreased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Protein total decreased
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Investigations
Red blood cell count decreased
|
0.00%
0/4
|
0.00%
0/12
|
8.2%
4/49 • Number of events 5
|
|
Investigations
Romberg test positive
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
Transaminases increased
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Investigations
Weight decreased
|
0.00%
0/4
|
0.00%
0/12
|
18.4%
9/49 • Number of events 10
|
|
Investigations
Weight increased
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Investigations
White blood cell count increased
|
0.00%
0/4
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
|
Metabolism and nutrition disorders
Decreased appetite
|
25.0%
1/4 • Number of events 1
|
58.3%
7/12 • Number of events 8
|
38.8%
19/49 • Number of events 24
|
|
Metabolism and nutrition disorders
Dehydration
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
12.2%
6/49 • Number of events 7
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
10.2%
5/49 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/4
|
41.7%
5/12 • Number of events 6
|
18.4%
9/49 • Number of events 11
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Musculoskeletal and connective tissue disorders
Clubbing
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
8.2%
4/49 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/4
|
8.3%
1/12 • Number of events 2
|
2.0%
1/49 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
25.0%
1/4 • Number of events 1
|
33.3%
4/12 • Number of events 4
|
4.1%
2/49 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/4
|
25.0%
3/12 • Number of events 4
|
6.1%
3/49 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Sjogren's syndrome
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/4
|
0.00%
0/12
|
6.1%
3/49 • Number of events 4
|
|
Nervous system disorders
Ataxia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Brachial plexopathy
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
50.0%
2/4 • Number of events 2
|
16.7%
2/12 • Number of events 2
|
12.2%
6/49 • Number of events 6
|
|
Nervous system disorders
Dysgeusia
|
25.0%
1/4 • Number of events 1
|
41.7%
5/12 • Number of events 5
|
6.1%
3/49 • Number of events 3
|
|
Nervous system disorders
Headache
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
12.2%
6/49 • Number of events 6
|
|
Nervous system disorders
Hypersomnia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Hypoaesthesia
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Nervous system disorders
Myoclonus
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Neurological decompensation
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Nervous system disorders
Sensory loss
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Nervous system disorders
Somnolence
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/4
|
0.00%
0/12
|
10.2%
5/49 • Number of events 5
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/4
|
0.00%
0/12
|
6.1%
3/49 • Number of events 3
|
|
Psychiatric disorders
Bruxism
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/4
|
0.00%
0/12
|
8.2%
4/49 • Number of events 4
|
|
Psychiatric disorders
Depression
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
4.1%
2/49 • Number of events 2
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Psychiatric disorders
Insomnia
|
25.0%
1/4 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
14.3%
7/49 • Number of events 7
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Renal and urinary disorders
Chromaturia
|
75.0%
3/4 • Number of events 3
|
75.0%
9/12 • Number of events 9
|
8.2%
4/49 • Number of events 4
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
0.00%
0/49
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Renal and urinary disorders
Micturition urgency
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Renal and urinary disorders
Nocturia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Renal and urinary disorders
Ureteric obstruction
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/29
|
|
Reproductive system and breast disorders
Gynaecomastia
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/29
|
|
Reproductive system and breast disorders
Menopausal symptoms
|
0.00%
0/4
|
0.00%
0/9
|
5.0%
1/20 • Number of events 1
|
|
Reproductive system and breast disorders
Vulvovaginal dryness
|
0.00%
0/4
|
11.1%
1/9 • Number of events 1
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/4
|
33.3%
4/12 • Number of events 4
|
28.6%
14/49 • Number of events 18
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
50.0%
2/4 • Number of events 2
|
50.0%
6/12 • Number of events 7
|
24.5%
12/49 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.0%
1/4 • Number of events 1
|
25.0%
3/12 • Number of events 3
|
8.2%
4/49 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
25.0%
1/4 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal oedema
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
25.0%
1/4 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
8.2%
4/49 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
1/4 • Number of events 1
|
25.0%
3/12 • Number of events 4
|
10.2%
5/49 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
25.0%
1/4 • Number of events 1
|
16.7%
2/12 • Number of events 2
|
12.2%
6/49 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
25.0%
1/4 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
25.0%
1/4 • Number of events 2
|
33.3%
4/12 • Number of events 4
|
20.4%
10/49 • Number of events 11
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
2.0%
1/49 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
25.0%
1/4 • Number of events 1
|
0.00%
0/12
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
50.0%
2/4 • Number of events 2
|
41.7%
5/12 • Number of events 8
|
14.3%
7/49 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
Rash
|
75.0%
3/4 • Number of events 3
|
75.0%
9/12 • Number of events 13
|
59.2%
29/49 • Number of events 36
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
6.1%
3/49 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Rash follicular
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Scab
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/4
|
16.7%
2/12 • Number of events 2
|
0.00%
0/49
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
4.1%
2/49 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/4
|
8.3%
1/12 • Number of events 2
|
0.00%
0/49
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/4
|
0.00%
0/12
|
2.0%
1/49 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.00%
0/4
|
0.00%
0/12
|
4.1%
2/49 • Number of events 2
|
|
Vascular disorders
Hypotension
|
0.00%
0/4
|
0.00%
0/12
|
8.2%
4/49 • Number of events 4
|
|
Vascular disorders
Thrombosis
|
0.00%
0/4
|
8.3%
1/12 • Number of events 1
|
0.00%
0/49
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60