Trial Outcomes & Findings for A Study of E7050 in Combination With E7080 in Participants With Advanced Solid Tumors (Dose Escalation) and in Participants With Recurrent Glioblastoma or Unresectable Stage III or Stage IV Melanoma After Prior Systemic Therapy (Expansion Cohort and Phase 2) (NCT NCT01433991)
NCT ID: NCT01433991
Last Updated: 2021-06-08
Results Overview
DLT was defined as toxicity related to the combination therapy and was graded according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Hematological DLTs were Grade 4 neutropenia for greater than or equal to (\>=) 7 days or Grade 3 neutropenia with fever (greater than \[\>\] 38.5 degree Celsius (°C) in axilla), Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or lasting \>7 days and decrease of hemoglobin of Grade 4. Non-hematological DLTS were Grade 3 fatigue, or a 2 point decline in Eastern Cooperative Oncology Group (ECOG) performance status must persist for \>7days, Nausea, vomiting or diarrhea must persist at Grade 3 or 4 despite maximal medical therapy, Grade 4 hypertension or Grade 3 hypertension not able to be controlled by medication and any Grade 3 or higher non-hematological laboratory abnormalities that require hospitalization.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Cycle 1 (Cycle length= 28 days)
Results posted on
2021-06-08
Participant Flow
Participants took part in the study at 2 investigative sites in the United States from 13 October 2011 to 01 March 2017.
A total of 40 participants were screened, of which 10 were screen failures and 30 participants were enrolled in the study. This study was planned to be conducted in 2 parts: Phase 1b part and Phase 2 part. Study was terminated by the sponsor at the end of Phase 1b due to a change in corporate strategy, hence Phase 2 was not carried out. In this study, a single agent run-in period was conducted prior to the administration of combination treatment in treatment phase.
Participant milestones
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
Participants received lenvatinib 12 milligram (mg) capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 300 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 400 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Pretreatment Phase (Single Agent Run-in)
STARTED
|
5
|
3
|
14
|
8
|
|
Pretreatment Phase (Single Agent Run-in)
COMPLETED
|
3
|
3
|
14
|
8
|
|
Pretreatment Phase (Single Agent Run-in)
NOT COMPLETED
|
2
|
0
|
0
|
0
|
|
Treatment Phase (Combination Agent)
STARTED
|
3
|
3
|
14
|
8
|
|
Treatment Phase (Combination Agent)
COMPLETED
|
1
|
2
|
8
|
2
|
|
Treatment Phase (Combination Agent)
NOT COMPLETED
|
2
|
1
|
6
|
6
|
Reasons for withdrawal
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
Participants received lenvatinib 12 milligram (mg) capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 300 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 400 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Pretreatment Phase (Single Agent Run-in)
Did not enter into treatment phase
|
2
|
0
|
0
|
0
|
|
Treatment Phase (Combination Agent)
Adverse Event
|
1
|
0
|
3
|
1
|
|
Treatment Phase (Combination Agent)
Lost to Follow-up
|
0
|
0
|
0
|
1
|
|
Treatment Phase (Combination Agent)
Participant Choice
|
0
|
0
|
0
|
1
|
|
Treatment Phase (Combination Agent)
Clinical progression
|
0
|
1
|
2
|
3
|
|
Treatment Phase (Combination Agent)
Progressive disease
|
1
|
0
|
0
|
0
|
|
Treatment Phase (Combination Agent)
Terminated by sponsor
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Study of E7050 in Combination With E7080 in Participants With Advanced Solid Tumors (Dose Escalation) and in Participants With Recurrent Glioblastoma or Unresectable Stage III or Stage IV Melanoma After Prior Systemic Therapy (Expansion Cohort and Phase 2)
Baseline characteristics by cohort
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Participants received lenvatinib 12 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 Participants
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 300 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 400 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
58.0 years
n=5 Participants
|
63.0 years
n=7 Participants
|
64.5 years
n=5 Participants
|
56.5 years
n=4 Participants
|
62.0 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (Cycle length= 28 days)Population: The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation. Here, overall number analyzed "N" were the participants who were evaluable for the outcome measure.
DLT was defined as toxicity related to the combination therapy and was graded according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Hematological DLTs were Grade 4 neutropenia for greater than or equal to (\>=) 7 days or Grade 3 neutropenia with fever (greater than \[\>\] 38.5 degree Celsius (°C) in axilla), Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or lasting \>7 days and decrease of hemoglobin of Grade 4. Non-hematological DLTS were Grade 3 fatigue, or a 2 point decline in Eastern Cooperative Oncology Group (ECOG) performance status must persist for \>7days, Nausea, vomiting or diarrhea must persist at Grade 3 or 4 despite maximal medical therapy, Grade 4 hypertension or Grade 3 hypertension not able to be controlled by medication and any Grade 3 or higher non-hematological laboratory abnormalities that require hospitalization.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)- Combination Treatment
|
0 Participants
|
0 Participants
|
4 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (Cycle length= 28 days)Population: The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.
The MTD was defined as the highest dose level at which no more than 1/6 participants experienced a DLTs, with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the dose escalation part. The RP2D of golvatinib in Combination with lenvatinib was MTD determined by Dose Escalation Committee (DEC) based on safety, PK and clinical data. DLT was defined as toxicity related to the combination therapy and was graded according to CTCAE v4.0.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=28 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Golvatinib in Combination With Lenvatinib
MTD
|
300.0 milligram per day (mg/day)
|
—
|
—
|
—
|
|
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Golvatinib in Combination With Lenvatinib
RP2D
|
300.0 milligram per day (mg/day)
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycle 1 (Cycle length= 28 days)Population: The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.
The MTD was defined as the highest dose level at which no more than 1/6 participants experienced a DLTs, with the next higher dose having at least 0 of 3 or 1 of 6 participants experiencing DLTs. MTD was determined by summarizing the number and percentage of participants with DLTs for the first cycle, by study dosing schedule, initial dosing level and overall for the dose escalation part. The RP2D of lenvatinib in Combination with golvatinib was MTD determined by DEC based on safety, PK and clinical data. DLT was defined as toxicity related to the combination therapy and was graded according to CTCAE v4.0.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=28 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Golvatinib
MTD
|
20.0 mg/day
|
—
|
—
|
—
|
|
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Lenvatinib in Combination With Golvatinib
RP2D
|
20.0 mg/day
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline up to approximately 5 years 5 monthsPopulation: The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values- Combination Treatment
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From baseline up to approximately 5 years 5 monthsPopulation: The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values- Combination Treatment
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From baseline up to approximately 5 years 5 monthsPopulation: The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values- Combination Treatment
At least 1 post-baseline increase of > 60 msec
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Phase 1b: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values- Combination Treatment
At least 1 post-baseline value of > 450 msec
|
2 Participants
|
2 Participants
|
8 Participants
|
4 Participants
|
|
Phase 1b: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values- Combination Treatment
At least 1 post-baseline value of > 480 msec
|
1 Participants
|
0 Participants
|
4 Participants
|
1 Participants
|
|
Phase 1b: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values- Combination Treatment
At least 1 post-baseline value of > 500 msec
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Phase 1b: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values- Combination Treatment
Baseline and post-baseline data
|
3 Participants
|
3 Participants
|
13 Participants
|
8 Participants
|
|
Phase 1b: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Values- Combination Treatment
At least 1 post-baseline increase of greater than (>) 30 millisecond (msec)
|
2 Participants
|
0 Participants
|
1 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: From baseline up to approximately up to 5 years 5 monthsPopulation: The safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)- Combination Treatment
TEAEs
|
3 Participants
|
3 Participants
|
14 Participants
|
8 Participants
|
|
Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)- Combination Treatment
SAEs
|
2 Participants
|
1 Participants
|
8 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Day -7: 0-24 hours post-dosePopulation: The pharmacokinetic (PK) analysis set included participants who had at least 1 evaluable plasma concentration.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Cmax; Maximum Observed Plasma Concentration for Golvatinib When Administered as a Single Agent at Day -7
|
2160 nanograms per milliliter (ng/mL)
Standard Deviation 848
|
1710 nanograms per milliliter (ng/mL)
Standard Deviation 1410
|
3020 nanograms per milliliter (ng/mL)
Standard Deviation 2130
|
3930 nanograms per milliliter (ng/mL)
Standard Deviation 1800
|
SECONDARY outcome
Timeframe: Day -8: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Cmax; Maximum Observed Plasma Concentration for Lenvatinib When Administered as a Single Agent at Day -8
|
174 ng/mL
Standard Deviation 88.0
|
393 ng/mL
Standard Deviation 75.0
|
297 ng/mL
Standard Deviation 159
|
388 ng/mL
Standard Deviation 250
|
SECONDARY outcome
Timeframe: Day -7: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered as a Single Agent at Day -7
|
2.00 hours
Interval 1.43 to 11.6
|
4.00 hours
Interval 3.02 to 4.08
|
2.54 hours
Interval 1.95 to 4.08
|
2.54 hours
Interval 1.98 to 7.92
|
SECONDARY outcome
Timeframe: Day -8: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Lenvatinib When Administered as a Single Agent at Day -8
|
3.00 hours
Interval 1.0 to 3.08
|
2.00 hours
Interval 2.0 to 2.92
|
3.01 hours
Interval 1.93 to 8.0
|
3.00 hours
Interval 1.0 to 23.5
|
SECONDARY outcome
Timeframe: Day -7: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here, overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=4 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Golvatinib When Administered as Single Agent at Day -7
|
25600 nanogram*hour per milliliter(ng*h/mL)
Standard Deviation 6720
|
19300 nanogram*hour per milliliter(ng*h/mL)
Standard Deviation 14000
|
34400 nanogram*hour per milliliter(ng*h/mL)
Standard Deviation 25600
|
50000 nanogram*hour per milliliter(ng*h/mL)
Standard Deviation 27900
|
SECONDARY outcome
Timeframe: Day -8: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Lenvatinib When Administered as Single Agent at Day -8
|
1540 ng*h/mL
Standard Deviation 581
|
2690 ng*h/mL
Standard Deviation 75.7
|
2620 ng*h/mL
Standard Deviation 1160
|
3200 ng*h/mL
Standard Deviation 2210
|
SECONDARY outcome
Timeframe: Day -7: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered as Single Agent at Day -7
|
26500 ng*h/mL
Standard Deviation 6380
|
34700 ng*h/mL
Standard Deviation 27900
|
38000 ng*h/mL
Standard Deviation 25400
|
64000 ng*h/mL
Standard Deviation 33000
|
SECONDARY outcome
Timeframe: Day -8: 0-24 hours post-dosePopulation: PK analysis set included participants who had at least 1 evaluable plasma concentration.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Lenvatinib When Administered as Single Agent at Day -8
|
1800 ng*h/mL
Standard Deviation 697
|
3030 ng*h/mL
Standard Deviation 254
|
3030 ng*h/mL
Standard Deviation 1260
|
3780 ng*h/mL
Standard Deviation 2630
|
SECONDARY outcome
Timeframe: Day -7: 0-24 hours post-dosePopulation: PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUC∞; Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for Golvatinib When Administered as Single Agent at Day -7
|
—
|
58300 ng*h/mL
Standard Deviation 23500
|
51200 ng*h/mL
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
—
|
SECONDARY outcome
Timeframe: Day -8: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here, overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUC∞; Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value for the Last Quantifiable Concentration for Lenvatinib When Administered as Single Agent at Day -8
|
1890 ng*h/mL
Standard Deviation 693
|
3060 ng*h/mL
Standard Deviation 250
|
2930 ng*h/mL
Standard Deviation 1360
|
3910 ng*h/mL
Standard Deviation 2680
|
SECONDARY outcome
Timeframe: Day-7: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: t1/2; Terminal Elimination Half-life for Golvatinib When Administered as Single Agent at Day -7
|
—
|
34.6 hours
Standard Deviation 1.77
|
30.7 hours
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
57.0 hours
Standard Deviation 1.70
|
SECONDARY outcome
Timeframe: Day -8: 0-24 hours post-dosePopulation: PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: t1/2; Terminal Elimination Half-life for Lenvatinib When Administered as Single Agent at Day -8
|
11.2 hours
Standard Deviation 3.27
|
14.6 hours
Standard Deviation 6.69
|
12.0 hours
Standard Deviation 5.49
|
14.4 hours
Standard Deviation 6.86
|
SECONDARY outcome
Timeframe: Day -7: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: CL/F; Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration for Golvatinib When Administered as Single Agent at Day -7
|
—
|
3.74 liter per hour (L/h)
Standard Deviation 1.51
|
5.87 liter per hour (L/h)
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
—
|
SECONDARY outcome
Timeframe: Day -8: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: CL/F; Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration for Lenvatinib When Administered as Single Agent at Day -8
|
7.01 liter per hour (L/h)
Standard Deviation 2.31
|
6.57 liter per hour (L/h)
Standard Deviation 0.556
|
8.63 liter per hour (L/h)
Standard Deviation 5.33
|
7.23 liter per hour (L/h)
Standard Deviation 4.25
|
SECONDARY outcome
Timeframe: Day -7: 0-24 hours post-dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Vz/F; Apparent Volume of Distribution at Terminal Phase for Golvatinib When Administered as Single Agent at Day -7
|
—
|
188 liter (L)
Standard Deviation 84.9
|
260 liter (L)
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
—
|
SECONDARY outcome
Timeframe: Day -8: 0-24 hours post dosePopulation: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Vz/F; Apparent Volume of Distribution at Terminal Phase for Lenvatinib When Administered as Single Agent at Day -8
|
112 liter (L)
Standard Deviation 53.4
|
135 liter (L)
Standard Deviation 55.1
|
182 liter (L)
Standard Deviation 209
|
137 liter (L)
Standard Deviation 87.5
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Cmax; Maximum Observed Plasma Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1
Golvatinib: Cycle 1 Day 1
|
2890 ng/mL
Standard Deviation 1080
|
1990 ng/mL
Standard Deviation 1470
|
3050 ng/mL
Standard Deviation 1030
|
4820 ng/mL
Standard Deviation 1510
|
|
Phase 1b: Cmax; Maximum Observed Plasma Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1
Lenvatinib: Cycle 1 Day 1
|
182 ng/mL
Standard Deviation 137
|
315 ng/mL
Standard Deviation 35.4
|
258 ng/mL
Standard Deviation 148
|
251 ng/mL
Standard Deviation 144
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=4 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Cmax; Maximum Observed Plasma Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Golvatinib: Cycle 2 Day 1
|
3540 ng/mL
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
2750 ng/mL
Standard Deviation 870
|
3570 ng/mL
Standard Deviation 1350
|
6920 ng/mL
Standard Deviation 4130
|
|
Phase 1b: Cmax; Maximum Observed Plasma Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Lenvatinib: Cycle 2 Day 1
|
66.3 ng/mL
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
356 ng/mL
Standard Deviation 76.4
|
245 ng/mL
Standard Deviation 110
|
408 ng/mL
Standard Deviation 250
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1
Golvatinib: Cycle 1 Day 1
|
3.02 hours
Interval 2.12 to 4.02
|
4.00 hours
Interval 2.03 to 4.08
|
3.52 hours
Interval 1.98 to 8.05
|
3.00 hours
Interval 0.98 to 4.13
|
|
Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1
Lenvatinib: Cycle 1 Day 1
|
3.02 hours
Interval 2.12 to 4.02
|
2.02 hours
Interval 2.0 to 2.03
|
3.95 hours
Interval 1.98 to 4.03
|
3.98 hours
Interval 2.0 to 4.13
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=4 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Golvatinib: Cycle 2 Day 1
|
8.05 hours
Interval 8.05 to 8.05
|
2.00 hours
Interval 1.0 to 3.0
|
2.97 hours
Interval 1.02 to 3.97
|
3.53 hours
Interval 3.0 to 7.92
|
|
Phase 1b: Tmax; Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Lenvatinib: Cycle 2 Day 1
|
10.55 hours
Interval 10.55 to 10.55
|
3.00 hours
Interval 2.0 to 4.0
|
3.90 hours
Interval 2.03 to 3.97
|
3.53 hours
Interval 2.0 to 7.92
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1
Golvatinib: Cycle 1 Day 1
|
33800 ng*h/mL
Standard Deviation 4270
|
22100 ng*h/mL
Standard Deviation 15900
|
38700 ng*h/mL
Standard Deviation 21700
|
60400 ng*h/mL
Standard Deviation 26200
|
|
Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1
Lenvatinib: Cycle 1 Day 1
|
1460 ng*h/mL
Standard Deviation 922
|
2370 ng*h/mL
Standard Deviation 35.4
|
2290 ng*h/mL
Standard Deviation 1250
|
2390 ng*h/mL
Standard Deviation 1710
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=4 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Golvatinib: Cycle 2 Day 1
|
68700 ng*h/mL
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
45000 ng*h/mL
Standard Deviation 29700
|
57100 ng*h/mL
Standard Deviation 25300
|
138000 ng*h/mL
Standard Deviation 98900
|
|
Phase 1b: AUC24; Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Lenvatinib: Cycle 2 Day 1
|
1120 ng*h/mL
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
3060 ng*h/mL
Standard Deviation 247
|
2380 ng*h/mL
Standard Deviation 1430
|
4320 ng*h/mL
Standard Deviation 3860
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=6 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1
Golvatinib: Cycle 1 Day 1
|
34000 ng*h/mL
Standard Deviation 4290
|
22200 ng*h/mL
Standard Deviation 15900
|
39800 ng*h/mL
Standard Deviation 21800
|
60800 ng*h/mL
Standard Deviation 26700
|
|
Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib and Lenvatinib When Administered in Combination Treatment as Single Dose on Day 1 Cycle 1
Lenvatinib: Cycle 1 Day 1
|
1470 ng*h/mL
Standard Deviation 921
|
2370 ng*h/mL
Standard Deviation 42.4
|
2400 ng*h/mL
Standard Deviation 1270
|
2400 ng*h/mL
Standard Deviation 1730
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=4 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Golvatinib: Cycle 2 Day 1
|
68700 ng*h/mL
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
45200 ng*h/mL
Standard Deviation 29500
|
57100 ng*h/mL
Standard Deviation 25300
|
138000 ng*h/mL
Standard Deviation 98700
|
|
Phase 1b: AUCt; Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Lenvatinib: Cycle 2 Day 1
|
1120 ng*h/mL
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
3060 ng*h/mL
Standard Deviation 255
|
2380 ng*h/mL
Standard Deviation 1430
|
4330 ng*h/mL
Standard Deviation 3850
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: CLss/F; Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Golvatinib: Cycle 2 Day 1
|
—
|
5.69 liter per hour (L/h)
Standard Deviation 3.76
|
—
|
3.49 liter per hour (L/h)
Standard Deviation 1.81
|
|
Phase 1b: CLss/F; Apparent Clearance After Extravascular Administration Calculated Using the Observed Value of the Last Quantifiable Concentration for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Lenvatinib: Cycle 2 Day 1
|
—
|
6.58 liter per hour (L/h)
Standard Deviation 0.54
|
—
|
7.96 liter per hour (L/h)
Standard Deviation 5.72
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=4 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Rac(AUC); Accumulation Ratio Based on AUC Calculated as AUC24 at Steady State/AUC24 for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Golvatinib: Cycle 2 Day 1
|
2.35 ratio
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
3.96 ratio
Standard Deviation 2.14
|
1.90 ratio
Standard Deviation 0.905
|
2.10 ratio
Standard Deviation 0.254
|
|
Phase 1b: Rac(AUC); Accumulation Ratio Based on AUC Calculated as AUC24 at Steady State/AUC24 for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Lenvatinib: Cycle 2 Day 1
|
1.88 ratio
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
1.29 ratio
Standard Deviation 0.127
|
0.928 ratio
Standard Deviation 0.295
|
1.61 ratio
Standard Deviation 0.670
|
SECONDARY outcome
Timeframe: Cycle 2 Day 1: 0-24 hours post-dose (cycle length is 28 days)Population: The PK analysis set included participants who had at least 1 evaluable plasma concentration. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given time points.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=1 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=2 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=5 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=4 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Rac(Cmax); Accumulation Ratio Based on Cmax Calculated as Cmax at Steady State/Cmax for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Golvatinib: Cycle 2 Day 1
|
2.11 ratio
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
3.16 ratio
Standard Deviation 2.24
|
1.30 ratio
Standard Deviation 0.481
|
1.49 ratio
Standard Deviation 0.319
|
|
Phase 1b: Rac(Cmax); Accumulation Ratio Based on Cmax Calculated as Cmax at Steady State/Cmax for Golvatinib and Lenvatinib When Administered in Combination Treatment as Multiple Dose on Day 1 Cycle 2
Lenvatinib: Cycle 2 Day 1
|
1.44 ratio
Standard Deviation NA
Standard deviation could not be calculated because only one participant was available for evaluation.
|
1.13 ratio
Standard Deviation 0.120
|
1.17 ratio
Standard Deviation 0.556
|
1.63 ratio
Standard Deviation 1.27
|
SECONDARY outcome
Timeframe: From the date of the first dose of study drug to the date of the first documentation of disease progression or death, whichever occurred first (approximately up to 5 years 5 months)Population: Safety analysis set (combination treatment) included all participants who received at least 1 dose of combination treatment and had at least 1 postbaseline safety evaluation.
ORR was assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. ORR was defined as the percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<)10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Outcome measures
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 Participants
Eligible participants from single agent run-in period, received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles in combination agent treatment period until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Phase 1b: Objective Response Rate (ORR); Combination Treatment
|
0 percentage of participants
The 95% confidence interval could not be estimated due to insufficient number of participants with event during the study.
|
0 percentage of participants
The 95% confidence interval could not be estimated due to insufficient number of participants with event during the study.
|
28.6 percentage of participants
Interval 8.4 to 58.1
|
12.5 percentage of participants
Interval 0.3 to 52.7
|
Adverse Events
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 1 deaths
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 1 deaths
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
Serious events: 8 serious events
Other events: 13 other events
Deaths: 0 deaths
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
Serious events: 3 serious events
Other events: 8 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 participants at risk
Participants received lenvatinib 12 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 participants at risk
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 participants at risk
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 300 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 participants at risk
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 400 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Abdominal Pain Lower
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Intestinal Perforation
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Large Intestinal Obstruction
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Device Occlusion
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Fatigue
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Pyrexia
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Lung Infection
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Hepatobiliary disorders
Bile Duct Obstruction
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Vascular disorders
Hypertension
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Electrocardiogram Qt Prolonged
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Pleural Effusion
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Syncope
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Renal and urinary disorders
Renal Failure Acute
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Urinary tract infection enterococcal
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
Other adverse events
| Measure |
Cohort 1: Lenvatinib 12 mg + Golvatinib 200 mg
n=3 participants at risk
Participants received lenvatinib 12 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 12 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 2: Lenvatinib 20 mg + Golvatinib 200 mg
n=3 participants at risk
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 200 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 200 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 3: Lenvatinib 20 mg + Golvatinib 300 mg
n=14 participants at risk
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 300 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 300 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
Cohort 4: Lenvatinib 20 mg + Golvatinib 400 mg
n=8 participants at risk
Participants received lenvatinib 20 mg capsules, orally, once on Day -8, followed by golvatinib 400 mg tablets, orally, once on Day -7 in single agent run in period. Eligible participants who completed run-in period were then entered in combination agent treatment period. In combination agent treatment period, participants received lenvatinib 20 mg capsules, orally, once daily in combination with golvatinib 400 mg tablets, orally, once daily in 28-days treatment cycles until disease progression, development of unacceptable toxicity, or withdrawal of consent (up to approximately 88 weeks).
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
92.9%
13/14 • From baseline up to approximately 5 years 5 months
|
62.5%
5/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Vomiting
|
100.0%
3/3 • From baseline up to approximately 5 years 5 months
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
64.3%
9/14 • From baseline up to approximately 5 years 5 months
|
75.0%
6/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Abdominal Pain
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
35.7%
5/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
57.1%
8/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Oral Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Abdominal Distension
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Dry Mouth
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Anal Haemorrhage
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Gastrointestinal Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Glossodynia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Lip Dry
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Oesophageal Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Tongue Discolouration
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Tongue Geographic
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Fatigue
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
100.0%
3/3 • From baseline up to approximately 5 years 5 months
|
78.6%
11/14 • From baseline up to approximately 5 years 5 months
|
62.5%
5/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Oedema Peripheral
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Chills
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Asthenia
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Pyrexia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Influenza Like Illness
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Injection Site Nodule
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Injection Site Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Injection Site Swelling
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Malaise
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Peripheral Swelling
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
General disorders
Suprapubic Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
100.0%
3/3 • From baseline up to approximately 5 years 5 months
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
71.4%
10/14 • From baseline up to approximately 5 years 5 months
|
62.5%
5/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Dehydration
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
50.0%
7/14 • From baseline up to approximately 5 years 5 months
|
50.0%
4/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
42.9%
6/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
35.7%
5/14 • From baseline up to approximately 5 years 5 months
|
50.0%
4/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
100.0%
3/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
42.9%
6/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea Exertional
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Increased Upper Airway Secretion
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Aspartate Aminotransferase Increased
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
71.4%
10/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
57.1%
8/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Lipase Increased
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Electrocardiogram Qt Prolonged
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Weight Decreased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
White Blood Cell Count Decreased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Neutrophil Count Decreased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Platelet Count Decreased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Amylase Increased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Groin Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Muscle Twitching
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Discomfort
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Tendon Discomfort
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Blood Albumin Decreased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Blood Creatinine Increased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Blood Sodium Decreased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Blood Thyroid Stimulating Hormone Decreased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Blood Thyroid Stimulating Hormone Increased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Clostridium Test Positive
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Dizziness
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Tremor
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Memory Impairment
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Syncope
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Lethargy
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Mental Impairment
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Migraine
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Nervous system disorders
Presyncope
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Vascular disorders
Hypertension
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
42.9%
6/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Vascular disorders
Hot Flush
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Vascular disorders
Hypotension
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Vascular disorders
Orthostatic Hypotension
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
42.9%
6/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Pneumonia
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Abdominal Abscess
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Bacteriuria
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Bronchitis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Clostridium Difficile Colitis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Fungal Infection
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Herpes Simplex
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Kidney Infection
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Oral Infection
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Sinusitis Bacterial
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
21.4%
3/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis Acneiform
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Decubitus Ulcer
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Hair Colour Changes
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Rash Papular
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Skin Discolouration
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Skin and subcutaneous tissue disorders
Skin Irritation
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
35.7%
5/14 • From baseline up to approximately 5 years 5 months
|
50.0%
4/8 • From baseline up to approximately 5 years 5 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
50.0%
7/14 • From baseline up to approximately 5 years 5 months
|
37.5%
3/8 • From baseline up to approximately 5 years 5 months
|
|
Renal and urinary disorders
Proteinuria
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
50.0%
7/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
14.3%
2/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Renal and urinary disorders
Nocturia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Renal and urinary disorders
Renal Failure Acute
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Renal and urinary disorders
Urinary Retention
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Psychiatric disorders
Insomnia
|
66.7%
2/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
28.6%
4/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Psychiatric disorders
Agitation
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Psychiatric disorders
Anxiety
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Psychiatric disorders
Confusional State
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Psychiatric disorders
Depression
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Psychiatric disorders
Hallucination, Auditory
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Psychiatric disorders
Mental Status Changes
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Psychiatric disorders
Panic Attack
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Cardiac disorders
Arteriosclerosis Coronary Artery
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Eye disorders
Dry Eye
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Eye disorders
Lacrimation Increased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Eye disorders
Photophobia
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Eye disorders
Strabismus
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Injury, poisoning and procedural complications
Stoma Site Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Injury, poisoning and procedural complications
Ligament Sprain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Injury, poisoning and procedural complications
Stoma Site Haemorrhage
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Ear and labyrinth disorders
Ear Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Ear and labyrinth disorders
Hearing Impaired
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Pleural Effusion
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Reproductive system and breast disorders
Pelvic Pain
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Reproductive system and breast disorders
Vaginal Haemorrhage
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Immune system disorders
Allergic Oedema
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Stoma Site Infection
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Activated Partial Thromboplastin Time Prolonged
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Blood Bilirubin Increased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Ejection Fraction Decreased
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Nausea
|
100.0%
3/3 • From baseline up to approximately 5 years 5 months
|
100.0%
3/3 • From baseline up to approximately 5 years 5 months
|
50.0%
7/14 • From baseline up to approximately 5 years 5 months
|
50.0%
4/8 • From baseline up to approximately 5 years 5 months
|
|
Gastrointestinal disorders
Small Intestinal Obstruction
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
0.00%
0/8 • From baseline up to approximately 5 years 5 months
|
|
Infections and infestations
Cytomegalovirus Gastrointestinal Infection
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
7.1%
1/14 • From baseline up to approximately 5 years 5 months
|
12.5%
1/8 • From baseline up to approximately 5 years 5 months
|
|
Investigations
Alanine Aminotransferase Increased
|
33.3%
1/3 • From baseline up to approximately 5 years 5 months
|
0.00%
0/3 • From baseline up to approximately 5 years 5 months
|
57.1%
8/14 • From baseline up to approximately 5 years 5 months
|
25.0%
2/8 • From baseline up to approximately 5 years 5 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place