Trial Outcomes & Findings for A Study in Healthy Volunteers to Compare the Pharmacokinetics of Sotorasib Administered as 1 or 2 Tablets (NCT NCT05327491)
NCT ID: NCT05327491
Last Updated: 2023-12-14
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
146 participants
Primary outcome timeframe
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of each period (Days 1 and 4)
Results posted on
2023-12-14
Participant Flow
A total of 146 participants were enrolled with all participants randomized into Treatment Sequences AB and BA, including 14 participants that proceeded to receive Treatment C in the food effect substudy.
Participant milestones
| Measure |
Treatment Sequence AB
Participants received a single oral dose of sotorasib under fasted conditions in the following order:
Period 1 - as 1 tablet (test 1) on Day 1 Period 2 - as 2 tablets (reference) on Day 4
|
Treatment Sequence BA
Participants received a single oral dose of sotorasib under fasted conditions in the following order:
Period 1 - as 2 tablets (reference) on Day 1 Period 2 - as 1 tablet (test 1) on Day 4
|
Treatment Sequence ABC
Participants who received treatment sequence AB in Periods 1 \& 2 proceeded to receive a single oral dose of sotorasib administered as 1 tablet with a high-fat meal in Period 3 on Day 7.
|
Treatment Sequence BAC
Participants who received treatment sequence BA in Periods 1 \& 2 proceeded to receive a single oral dose of sotorasib administered as 1 tablet with a high-fat meal in Period 3 on Day 7.
|
|---|---|---|---|---|
|
Periods 1 & 2
STARTED
|
73
|
73
|
0
|
0
|
|
Periods 1 & 2
Received at Least 1 Dose
|
73
|
73
|
0
|
0
|
|
Periods 1 & 2
COMPLETED
|
72
|
72
|
0
|
0
|
|
Periods 1 & 2
NOT COMPLETED
|
1
|
1
|
0
|
0
|
|
Period 3 (Food Effect Substudy)
STARTED
|
0
|
0
|
7
|
7
|
|
Period 3 (Food Effect Substudy)
COMPLETED
|
0
|
0
|
7
|
7
|
|
Period 3 (Food Effect Substudy)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence AB
Participants received a single oral dose of sotorasib under fasted conditions in the following order:
Period 1 - as 1 tablet (test 1) on Day 1 Period 2 - as 2 tablets (reference) on Day 4
|
Treatment Sequence BA
Participants received a single oral dose of sotorasib under fasted conditions in the following order:
Period 1 - as 2 tablets (reference) on Day 1 Period 2 - as 1 tablet (test 1) on Day 4
|
Treatment Sequence ABC
Participants who received treatment sequence AB in Periods 1 \& 2 proceeded to receive a single oral dose of sotorasib administered as 1 tablet with a high-fat meal in Period 3 on Day 7.
|
Treatment Sequence BAC
Participants who received treatment sequence BA in Periods 1 \& 2 proceeded to receive a single oral dose of sotorasib administered as 1 tablet with a high-fat meal in Period 3 on Day 7.
|
|---|---|---|---|---|
|
Periods 1 & 2
Miscellaneous
|
0
|
1
|
0
|
0
|
|
Periods 1 & 2
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Study in Healthy Volunteers to Compare the Pharmacokinetics of Sotorasib Administered as 1 or 2 Tablets
Baseline characteristics by cohort
| Measure |
Treatment Sequence AB
n=73 Participants
Participants received a single oral dose of sotorasib under fasted conditions in the following order:
Period 1 - as 1 tablet (test 1) on Day 1 Period 2 - as 2 tablets (reference) on Day 4
|
Treatment Sequence BA
n=73 Participants
Participants received a single oral dose of sotorasib under fasted conditions in the following order:
Period 1 - as 2 tablets (reference) on Day 1 Period 2 - as 1 tablet (test 1) on Day 4
|
Total
n=146 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.6 Years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
39.2 Years
STANDARD_DEVIATION 10.74 • n=7 Participants
|
38.4 Years
STANDARD_DEVIATION 10.91 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
67 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
30 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
43 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
41 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
85 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black and African American
|
27 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of each period (Days 1 and 4)Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
Outcome measures
| Measure |
Treatment A
n=145 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 1 tablet in either Period 1 or Period 2.
|
Treatment B
n=145 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 2 tablets in either Period 1 or Period 2.
|
Treatment C
All participants who received a single oral dose of sotorasib as 1 tablet with a high-fat meal in Period 3.
|
|---|---|---|---|
|
Period 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Sotorasib
|
4170 ng/mL
Geometric Coefficient of Variation 75.0
|
4340 ng/mL
Geometric Coefficient of Variation 65.5
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of each period (Days 1 and 4)Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
Outcome measures
| Measure |
Treatment A
n=145 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 1 tablet in either Period 1 or Period 2.
|
Treatment B
n=145 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 2 tablets in either Period 1 or Period 2.
|
Treatment C
All participants who received a single oral dose of sotorasib as 1 tablet with a high-fat meal in Period 3.
|
|---|---|---|---|
|
Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib
|
15300 h*ng/mL
Geometric Coefficient of Variation 56.2
|
15800 h*ng/mL
Geometric Coefficient of Variation 54.6
|
—
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on on the 1st day of each period (Days 1 and 4)Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
Outcome measures
| Measure |
Treatment A
n=144 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 1 tablet in either Period 1 or Period 2.
|
Treatment B
n=145 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 2 tablets in either Period 1 or Period 2.
|
Treatment C
All participants who received a single oral dose of sotorasib as 1 tablet with a high-fat meal in Period 3.
|
|---|---|---|---|
|
Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sotorasib
|
15500 h*ng/mL
Geometric Coefficient of Variation 54.1
|
16100 h*ng/mL
Geometric Coefficient of Variation 52.8
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9A TEAE was defined as an adverse event (AE) that started during or after dosing, or started prior to dosing and increased in severity after dosing within each period. Clinically significant laboratory tests, 12-lead electrocardiogram (ECG), or vital sign results as assessed by the Investigator were also recorded as adverse events.
Outcome measures
| Measure |
Treatment A
n=146 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 1 tablet in either Period 1 or Period 2.
|
Treatment B
n=146 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 2 tablets in either Period 1 or Period 2.
|
Treatment C
n=14 Participants
All participants who received a single oral dose of sotorasib as 1 tablet with a high-fat meal in Period 3.
|
|---|---|---|---|
|
Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
|
3 Participants
|
10 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of Period 3 (Day 7)Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
Outcome measures
| Measure |
Treatment A
n=14 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 1 tablet in either Period 1 or Period 2.
|
Treatment B
All participants who received a single oral dose of sotorasib under fasted conditions as 2 tablets in either Period 1 or Period 2.
|
Treatment C
All participants who received a single oral dose of sotorasib as 1 tablet with a high-fat meal in Period 3.
|
|---|---|---|---|
|
Period 3: Cmax of Sotorasib
|
4530 ng/mL
Geometric Coefficient of Variation 14.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on on the 1st day of Period 3 (Day 7)Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
Outcome measures
| Measure |
Treatment A
n=14 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 1 tablet in either Period 1 or Period 2.
|
Treatment B
All participants who received a single oral dose of sotorasib under fasted conditions as 2 tablets in either Period 1 or Period 2.
|
Treatment C
All participants who received a single oral dose of sotorasib as 1 tablet with a high-fat meal in Period 3.
|
|---|---|---|---|
|
Period 3: AUClast of Sotorasib
|
19000 h*ng/mL
Geometric Coefficient of Variation 20.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of Period 3 (Day 7)Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
Outcome measures
| Measure |
Treatment A
n=14 Participants
All participants who received a single oral dose of sotorasib under fasted conditions as 1 tablet in either Period 1 or Period 2.
|
Treatment B
All participants who received a single oral dose of sotorasib under fasted conditions as 2 tablets in either Period 1 or Period 2.
|
Treatment C
All participants who received a single oral dose of sotorasib as 1 tablet with a high-fat meal in Period 3.
|
|---|---|---|---|
|
Period 3: AUCinf of Sotorasib
|
19100 h*ng/mL
Geometric Coefficient of Variation 20.0
|
—
|
—
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Treatment B
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Treatment C
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=146 participants at risk
All participants who received a single oral dose of sotorasib under fasted conditions as 1 tablet in either Period 1 or Period 2.
|
Treatment B
n=146 participants at risk
All participants who received a single oral dose of sotorasib under fasted conditions as 2 tablets in either Period 1 or Period 2.
|
Treatment C
n=14 participants at risk
All participants who received a single oral dose of sotorasib as 1 tablet with a high-fat meal in Period 3.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/146 • Day 1 to Day 9
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/146 • Day 1 to Day 9
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/146 • Day 1 to Day 9
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/146 • Day 1 to Day 9
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/146 • Day 1 to Day 9
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
General disorders
Feeling cold
|
0.00%
0/146 • Day 1 to Day 9
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/146 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/146 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Nervous system disorders
Dizziness
|
0.00%
0/146 • Day 1 to Day 9
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Nervous system disorders
Headache
|
0.00%
0/146 • Day 1 to Day 9
|
2.1%
3/146 • Number of events 3 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Nervous system disorders
Presyncope
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/146 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/146 • Day 1 to Day 9
|
1.4%
2/146 • Number of events 2 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/146 • Day 1 to Day 9
|
0.68%
1/146 • Number of events 1 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
|
Vascular disorders
Haematoma
|
0.00%
0/146 • Day 1 to Day 9
|
1.4%
2/146 • Number of events 2 • Day 1 to Day 9
|
0.00%
0/14 • Day 1 to Day 9
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER