Trial Outcomes & Findings for A Study of LY2940680 in Small Cell Lung Cancer (NCT NCT01722292)
NCT ID: NCT01722292
Last Updated: 2018-12-28
Results Overview
MTD was defined as the highest tested dose that has \<33% probability of causing a dose-limiting toxicity(DLT). DLT was defined as an AE during Cycle 1 that is possibly related to the study drug and fulfills any one of the following criterion using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE),version 4.0:Grade 3 non-hematological toxicity except nausea, vomiting, constipation, diarrhea, fatigue, or anorexia that is manageable with appropriate care,transient(i.e., ≤5 days) Grade 3 elevations of alanine aminotransferase(ALT) and/or aspartate aminotransferase(AST), without evidence of other hepatic injury, in the setting of preexisting hepatic metastasis, ≥Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia of any duration,CTCAE Grade 4 hematological toxicity of \>5 days duration and any febrile neutropenia. any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose-limiting.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
26 participants
Primary outcome timeframe
Baseline to Completion of the Phase 1b (Up To 12 Months)
Results posted on
2018-12-28
Participant Flow
Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped. Phase 1b study completer was defined as completion of the dose-limiting toxicity (DLT) period (1 cycle- 21 days cycle for LY2940680 in combination with carboplatin and etoposide.
Participant milestones
| Measure |
Phase 1b: 100 mg LY2940680 + C + E
100 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve (AUC) 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
Maintenance:
Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
|
Phase 1b: 200 mg LY2940680 + C + E
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve (AUC) 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
Maintenance:
Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
|
Phase 1B: 400 mg LY2940680 + C + E
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve (AUC) 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
Maintenance:
Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
14
|
|
Overall Study
Received at Least One Dose of Study Drug
|
6
|
6
|
14
|
|
Overall Study
COMPLETED
|
6
|
6
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of LY2940680 in Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Phase 1b: 100 mg LY2940680 + C +E
n=6 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
Maintenance:
Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
|
Phase 1b: 200 mg LY2940680 + C + E
n=6 Participants
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
Maintenance:
Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
|
Phase 1b: 400 mg LY2940680 + C + E
n=14 Participants
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 milligrams\*minute\*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
Maintenance:
Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
64.3 years
STANDARD_DEVIATION 9.35 • n=5 Participants
|
64.8 years
STANDARD_DEVIATION 11.96 • n=7 Participants
|
60.2 years
STANDARD_DEVIATION 12.19 • n=5 Participants
|
62.2 years
STANDARD_DEVIATION 11.33 • n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
20 participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
6 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Completion of the Phase 1b (Up To 12 Months)Population: All participants who received at least one dose of study drug and were enrolled in Phase1b of the study.
MTD was defined as the highest tested dose that has \<33% probability of causing a dose-limiting toxicity(DLT). DLT was defined as an AE during Cycle 1 that is possibly related to the study drug and fulfills any one of the following criterion using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE),version 4.0:Grade 3 non-hematological toxicity except nausea, vomiting, constipation, diarrhea, fatigue, or anorexia that is manageable with appropriate care,transient(i.e., ≤5 days) Grade 3 elevations of alanine aminotransferase(ALT) and/or aspartate aminotransferase(AST), without evidence of other hepatic injury, in the setting of preexisting hepatic metastasis, ≥Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia of any duration,CTCAE Grade 4 hematological toxicity of \>5 days duration and any febrile neutropenia. any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose-limiting.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=26 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD)
|
—
|
400 milligrams (mg)
|
—
|
PRIMARY outcome
Timeframe: Randomization to Measured Progressive Disease or Death of Any Cause (Estimated as 18 Months)Population: Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hoursPopulation: All participants who received at least one dose of study drug and were enrolled in Phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
n=14 Participants
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=6 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
n=6 Participants
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose
LY2940680 Cycle 1, Day 1
|
1.56 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 35
|
0.491 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 64
|
1.01 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 36
|
|
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose
LY2940680 Cycle 2, Day 1
|
3.29 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 33
|
0.578 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 71
|
1.16 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 66
|
|
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose
LSN3185556 Cycle 1, Day 1
|
1.75 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 47
|
0.444 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 33
|
0.737 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 138
|
|
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose
LSN3185556 Cycle 2, Day 1
|
6 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 59
|
1.6 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 35
|
2.1 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 90
|
SECONDARY outcome
Timeframe: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hoursPopulation: All participants who received at least one dose of study drug and were enrolled in Phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped. C and E doses did not change for the 3 cohorts of LY (100,200 and 400 mg) so we only need to report one grouping.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=26 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose
Total Carboplatin Cycle 1, Day 1
|
—
|
16.7 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 33
|
—
|
|
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose
Total Carboplatin Cycle 2, Day 1
|
—
|
13.1 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 42
|
—
|
|
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose
Etoposide Cycle 1, Day 1
|
—
|
20.9 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 18
|
—
|
|
Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose
Etoposide Cycle 2, Day 1
|
—
|
18.4 microgram per milliliter (µg/mL)
Geometric Coefficient of Variation 28
|
—
|
SECONDARY outcome
Timeframe: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hoursPopulation: All participants who received at least one dose of study drug and were enrolled in phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
n=14 Participants
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=6 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
n=6 Participants
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose
LSN3185556 Cycle 1, Day 1
|
26 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 37
|
7.23 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 49
|
16.2 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 67
|
|
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose
LY2940680 Cycle 1, Day 1
|
15.9 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 27
|
6.34 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 57
|
8.96 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 39
|
|
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose
LY2940680 Cycle 2, Day 1
|
37.6 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 43
|
7.86 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 67
|
15.5 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 64
|
|
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose
LSN3185556 Cycle 2, Day 1
|
92.5 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 72
|
22.7 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 58
|
31.1 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 111
|
SECONDARY outcome
Timeframe: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hoursPopulation: All participants who received at least one dose of study drug and were enrolled in phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped. C and E doses did not change for the 3 cohorts of LY (100,200 and 400 mg) so we only need to report one grouping.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=26 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose
Total Carboplatin Cycle 1, Day 1
|
—
|
37.2 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 23
|
—
|
|
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose
Total Carboplatin Cycle 2, Day 1
|
—
|
32.0 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 25
|
—
|
|
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose
Etoposide Cycle 1, Day 1
|
—
|
104 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 22
|
—
|
|
Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose
Etoposide Cycle 2, Day 1
|
—
|
96.1 Hour*microgram per milliliter (h.µg/mL)
Geometric Coefficient of Variation 20
|
—
|
SECONDARY outcome
Timeframe: Baseline to Study Completion Up to 39 MonthsPopulation: All participants who received at least one dose of drug.
ORR was defined as the percentage of all randomized participants with the best overall response of PR or CR using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
n=14 Participants
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=6 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
n=6 Participants
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
|
57.1 percentage of participants
Interval 35.4 to 78.9
|
50 percentage of participants
Interval 16.4 to 83.6
|
50 percentage of participants
Interval 16.4 to 83.6
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2 Day 1, Cycle 7 Day 1Population: All participants who received at least one dose of drug and had samples available.
The gene expression data (Gli1) was normalized and the level of percentage of Gli1 inhibition post treatment was calculated.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
n=12 Participants
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=5 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
n=5 Participants
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells
|
94.8 Percentage of Gli 1 Inhibition
Interval 90.7 to 97.3
|
94.7 Percentage of Gli 1 Inhibition
Interval 75.9 to 94.9
|
95.1 Percentage of Gli 1 Inhibition
Interval 94.5 to 97.2
|
SECONDARY outcome
Timeframe: Randomization to Study Completion (Estimated as 38 Months)Population: Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Randomization to End of Cycle 2 (Estimated as 24 Months)Population: Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Randomization to Study Completion (Estimated as 38 Months)Population: Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hoursPopulation: All participants who received at least one dose of study drug and were enrolled in phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
n=14 Participants
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=6 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
n=6 Participants
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose
LY2940680 Cycle 1, Day 1
|
1.51 Hour (h)
Interval 0.5 to 6.0
|
2.05 Hour (h)
Interval 1.0 to 3.98
|
2.01 Hour (h)
Interval 1.03 to 2.05
|
|
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose
LY2940680 Cycle 2, Day 1
|
1 Hour (h)
Interval 0.5 to 6.0
|
2.96 Hour (h)
Interval 0.08 to 5.83
|
4 Hour (h)
Interval 1.88 to 4.08
|
|
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose
LSN3185556 Cycle 1, Day 2
|
6 Hour (h)
Interval 2.05 to 24.0
|
6.14 Hour (h)
Interval 2.0 to 24.03
|
5.87 Hour (h)
Interval 2.07 to 24.97
|
|
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose
LSN3185556 Cycle 2, Day 2
|
2.21 Hour (h)
Interval 0.5 to 6.0
|
2.3 Hour (h)
Interval 0.0 to 4.0
|
4.08 Hour (h)
Interval 4.0 to 23.83
|
SECONDARY outcome
Timeframe: Cycle (C)1 Day (D) 1:Predose,0.5 ,1, 2, 4, 6, 8h; C2 D1:Pr,0.5,1,2,4,6,8 hoursPopulation: All participants who received at least one dose of study drug and were enrolled in phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped. C and E doses did not change for the 3 cohorts of LY (100,200 and 400 mg) so we only need to report one grouping.
Outcome measures
| Measure |
Phase 1b: 400 mg LY2940680 + C+ E
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 100 mg LY2940680
n=26 Participants
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg\*min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose
Total Carboplatin Cycle 1, Day 1
|
—
|
0.5 Hour (h)
Interval 0.42 to 1.08
|
—
|
|
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose
Total Carboplatin Cycle 2, Day 1
|
—
|
0.5 Hour (h)
Interval 0.42 to 1.05
|
—
|
|
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose
Etoposide Cycle 1, Day 1
|
—
|
0.96 Hour (h)
Interval 0.48 to 1.5
|
—
|
|
Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose
Etoposide Cycle 2 ,Day 1
|
—
|
0.99 Hour (h)
Interval 0.33 to 1.17
|
—
|
Adverse Events
Phase 1b: 100 mg LY2940680 + C + E
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase 1b: 200 mg LY2940680 + C + E
Serious events: 6 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase 1b: 400 mg LY2940680 + C + E
Serious events: 8 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1b: 100 mg LY2940680 + C + E
n=6 participants at risk
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680 + C + E
n=6 participants at risk
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 400 mg LY2940680 + C + E
n=14 participants at risk
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Gastrointestinal disorders
Enterocolitis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
General disorders
Systemic inflammatory response syndrome
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
21.4%
3/14 • Number of events 3
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
0.00%
0/14
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Nervous system disorders
Nervous system disorder
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Vascular disorders
Hypovolaemic shock
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
Other adverse events
| Measure |
Phase 1b: 100 mg LY2940680 + C + E
n=6 participants at risk
100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 200 mg LY2940680 + C + E
n=6 participants at risk
200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
Phase 1b: 400 mg LY2940680 + C + E
n=14 participants at risk
400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m\^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.
Area under the Curve \[AUC\] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.
|
|---|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6 • Number of events 5
|
66.7%
4/6 • Number of events 6
|
35.7%
5/14 • Number of events 9
|
|
General disorders
Asthenia
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
7.1%
1/14 • Number of events 1
|
|
General disorders
Catheter site pain
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
General disorders
Fatigue
|
66.7%
4/6 • Number of events 4
|
50.0%
3/6 • Number of events 3
|
78.6%
11/14 • Number of events 15
|
|
General disorders
Gait disturbance
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
General disorders
Influenza like illness
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14 • Number of events 2
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14 • Number of events 2
|
|
General disorders
Oedema peripheral
|
16.7%
1/6 • Number of events 1
|
66.7%
4/6 • Number of events 4
|
14.3%
2/14 • Number of events 2
|
|
General disorders
Pyrexia
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Immune system disorders
Seasonal allergy
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Infections and infestations
Cellulitis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Infections and infestations
Escherichia urinary tract infection
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Folliculitis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Furuncle
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Infections and infestations
Gastrointestinal viral infection
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Blood and lymphatic system disorders
Anaemia
|
33.3%
2/6 • Number of events 3
|
50.0%
3/6 • Number of events 5
|
57.1%
8/14 • Number of events 12
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
83.3%
5/6 • Number of events 9
|
83.3%
5/6 • Number of events 8
|
50.0%
7/14 • Number of events 13
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
50.0%
3/6 • Number of events 6
|
50.0%
3/6 • Number of events 3
|
57.1%
8/14 • Number of events 14
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Cardiac disorders
Tachycardia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Eye disorders
Diplopia
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Eye disorders
Eyelid ptosis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
0.00%
0/14
|
|
Eye disorders
Visual impairment
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6
|
16.7%
1/6 • Number of events 2
|
14.3%
2/14 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
66.7%
4/6 • Number of events 4
|
16.7%
1/6 • Number of events 1
|
57.1%
8/14 • Number of events 10
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
42.9%
6/14 • Number of events 11
|
|
Gastrointestinal disorders
Dyspepsia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
7.1%
1/14 • Number of events 2
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
33.3%
2/6 • Number of events 2
|
66.7%
4/6 • Number of events 5
|
71.4%
10/14 • Number of events 13
|
|
Gastrointestinal disorders
Paraesthesia oral
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 3
|
14.3%
2/14 • Number of events 2
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Rash pustular
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Skin infection
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Infections and infestations
Tinea cruris
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14 • Number of events 2
|
|
Infections and infestations
Urinary tract infection bacterial
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Viral infection
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 2
|
|
Injury, poisoning and procedural complications
Fall
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Post procedural inflammation
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Sunburn
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Investigations
Blood creatinine increased
|
0.00%
0/6
|
16.7%
1/6 • Number of events 2
|
7.1%
1/14 • Number of events 2
|
|
Investigations
Blood potassium decreased
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Investigations
Creatinine renal clearance decreased
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
Investigations
Lipase increased
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Investigations
Platelet count decreased
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Investigations
Weight decreased
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
42.9%
6/14 • Number of events 7
|
|
Investigations
White blood cell count decreased
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
50.0%
3/6 • Number of events 3
|
50.0%
3/6 • Number of events 3
|
42.9%
6/14 • Number of events 7
|
|
Metabolism and nutrition disorders
Dehydration
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 3
|
0.00%
0/14
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
21.4%
3/14 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
16.7%
1/6 • Number of events 3
|
16.7%
1/6 • Number of events 1
|
14.3%
2/14 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypophagia
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6
|
16.7%
1/6 • Number of events 2
|
7.1%
1/14 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
66.7%
4/6 • Number of events 5
|
33.3%
2/6 • Number of events 3
|
42.9%
6/14 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
14.3%
2/14 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
Nervous system disorders
Aphasia
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Nervous system disorders
Cognitive disorder
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
21.4%
3/14 • Number of events 4
|
|
Nervous system disorders
Dizziness postural
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Nervous system disorders
Dysgeusia
|
66.7%
4/6 • Number of events 4
|
66.7%
4/6 • Number of events 4
|
57.1%
8/14 • Number of events 9
|
|
Nervous system disorders
Dyskinesia
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Nervous system disorders
Head discomfort
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Nervous system disorders
Neuropathy peripheral
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 2
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Nervous system disorders
Syncope
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14 • Number of events 2
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Nervous system disorders
Tremor
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Psychiatric disorders
Agitation
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
Psychiatric disorders
Depression
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
0.00%
0/14
|
|
Psychiatric disorders
Insomnia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
1/7 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.7%
1/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
21.4%
3/14 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
50.0%
3/6 • Number of events 3
|
33.3%
2/6 • Number of events 2
|
50.0%
7/14 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
21.4%
3/14 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Skin and subcutaneous tissue disorders
Skin plaque
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/14
|
|
Vascular disorders
Hypertension
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
7.1%
1/14 • Number of events 1
|
|
Vascular disorders
Hypotension
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/14
|
|
Vascular disorders
Orthostatic hypotension
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
0.00%
0/14
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60