Trial Outcomes & Findings for To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Patients With Hepatic Impairment and Healthy Subjects (NCT NCT02063230)
NCT ID: NCT02063230
Last Updated: 2016-07-21
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dose
Results posted on
2016-07-21
Participant Flow
Participant milestones
| Measure |
Mild
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
8
|
|
Overall Study
Received Treatment
|
8
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Patients With Hepatic Impairment and Healthy Subjects
Baseline characteristics by cohort
| Measure |
Mild
n=8 Participants
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
n=8 Participants
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
n=8 Participants
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
n=8 Participants
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
55 Years
STANDARD_DEVIATION 4 • n=5 Participants
|
57 Years
STANDARD_DEVIATION 5 • n=7 Participants
|
55 Years
STANDARD_DEVIATION 9 • n=5 Participants
|
57 Years
STANDARD_DEVIATION 7 • n=4 Participants
|
56 Years
STANDARD_DEVIATION 6 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dosePopulation: In the moderate group, 2 patients received Selumetinib 25mg and are not included here but are included in the Dose Normalised AUC outcome measure
Outcome measures
| Measure |
Mild
n=8 Participants
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
n=6 Participants
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
n=8 Participants
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
n=8 Participants
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
|---|---|---|---|---|
|
AUC (0 to Infinity) of Total Selumetinib
|
2300 ng*h/mL
Geometric Coefficient of Variation 38.9
|
4300 ng*h/mL
Geometric Coefficient of Variation 45.3
|
1680 ng*h/mL
Geometric Coefficient of Variation 19.9
|
2680 ng*h/mL
Geometric Coefficient of Variation 37.3
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dosePopulation: In the moderate group, 2 patients received Selumetinib 25mg and are not included here but are included in the Dose Normalised Cmax outcome measure
Outcome measures
| Measure |
Mild
n=8 Participants
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
n=6 Participants
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
n=8 Participants
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
n=8 Participants
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
|---|---|---|---|---|
|
Cmax of Total Selumetinib
|
741 ng/mL
Geometric Coefficient of Variation 47
|
1210 ng/mL
Geometric Coefficient of Variation 43.2
|
370 ng/mL
Geometric Coefficient of Variation 49.8
|
944 ng/mL
Geometric Coefficient of Variation 37.0
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post doseOutcome measures
| Measure |
Mild
n=8 Participants
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
n=8 Participants
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
n=8 Participants
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
n=8 Participants
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
|---|---|---|---|---|
|
Dose Normalized AUC, Total Selumetinib
|
45.9 ng*h/mL/mg
Geometric Coefficient of Variation 39.0
|
85.1 ng*h/mL/mg
Geometric Coefficient of Variation 38.3
|
84.3 ng*h/mL/mg
Geometric Coefficient of Variation 20.1
|
53.6 ng*h/mL/mg
Geometric Coefficient of Variation 37.3
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post doseOutcome measures
| Measure |
Mild
n=8 Participants
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
n=8 Participants
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
n=8 Participants
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
n=8 Participants
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
|---|---|---|---|---|
|
Dose Normalized Cmax, Total Selumetinib
|
14.8 ng/mL/mg
Geometric Coefficient of Variation 47.0
|
23.6 ng/mL/mg
Geometric Coefficient of Variation 37.4
|
18.5 ng/mL/mg
Geometric Coefficient of Variation 49.9
|
18.9 ng/mL/mg
Geometric Coefficient of Variation 37.0
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post doseOutcome measures
| Measure |
Mild
n=8 Participants
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
n=8 Participants
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
n=8 Participants
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
n=8 Participants
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
|---|---|---|---|---|
|
Dose Normalized AUC, Unbound Selumetinib
|
0.127 ng*h/mL/mg
Geometric Coefficient of Variation 41.4
|
0.259 ng*h/mL/mg
Geometric Coefficient of Variation 53.0
|
0.583 ng*h/mL/mg
Geometric Coefficient of Variation 44.9
|
0.184 ng*h/mL/mg
Geometric Coefficient of Variation 30.2
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post doseOutcome measures
| Measure |
Mild
n=8 Participants
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
n=8 Participants
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
n=8 Participants
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
n=8 Participants
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
|---|---|---|---|---|
|
Dose Normalized Cmax, Unbound Selumetinib
|
0.0409 ng/mL/mg
Geometric Coefficient of Variation 55.4
|
0.0716 ng/mL/mg
Geometric Coefficient of Variation 51.0
|
0.128 ng/mL/mg
Geometric Coefficient of Variation 73.0
|
0.0647 ng/mL/mg
Geometric Coefficient of Variation 32.0
|
Adverse Events
Mild
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Moderate
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Severe
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Normal
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Mild
n=8 participants at risk
Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)
|
Moderate
n=8 participants at risk
Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg
|
Severe
n=8 participants at risk
Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.
|
Normal
n=8 participants at risk
Healthy volunteers. All volunteers received Selumetinib 50mg.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
1/8 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
1/8 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
|
General disorders
Pyrexia
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
|
Injury, poisoning and procedural complications
Contusion
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
|
Nervous system disorders
Head Ache
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place