Trial Outcomes & Findings for A Study to Evaluate the Impact of Omeprazole on the Pharmacokinetics of Sotorasib Co-administered With an Acidic Beverage in Healthy Volunteers (NCT NCT05497557)
NCT ID: NCT05497557
Last Updated: 2024-01-19
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9
Results posted on
2024-01-19
Participant Flow
16 participants were enrolled at 1 center in the United States.
Participants were screened to assess their eligibility to enter the study within 28 days prior to the first dose administration.
Participant milestones
| Measure |
Sotorasib Alone
On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Omeprazole Alone
On Days 4 to 8, participants received 40 mg omeprazole (delayed release capsule) administered orally with 240 mL of water once daily (QD) after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Period 1: Sotorasib Alone
STARTED
|
16
|
0
|
0
|
|
Period 1: Sotorasib Alone
COMPLETED
|
16
|
0
|
0
|
|
Period 1: Sotorasib Alone
NOT COMPLETED
|
0
|
0
|
0
|
|
Period 2: Omeprazole Alone
STARTED
|
0
|
16
|
0
|
|
Period 2: Omeprazole Alone
COMPLETED
|
0
|
14
|
0
|
|
Period 2: Omeprazole Alone
NOT COMPLETED
|
0
|
2
|
0
|
|
Period 3: Omeprazole With Sotorasib
STARTED
|
0
|
0
|
14
|
|
Period 3: Omeprazole With Sotorasib
COMPLETED
|
0
|
0
|
14
|
|
Period 3: Omeprazole With Sotorasib
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sotorasib Alone
On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Omeprazole Alone
On Days 4 to 8, participants received 40 mg omeprazole (delayed release capsule) administered orally with 240 mL of water once daily (QD) after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Period 2: Omeprazole Alone
Withdrawal by Subject
|
0
|
2
|
0
|
Baseline Characteristics
A Study to Evaluate the Impact of Omeprazole on the Pharmacokinetics of Sotorasib Co-administered With an Acidic Beverage in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Sotorasib and Omeprazole: All Participants
n=16 Participants
On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours. On Days 4 to 8, participants received 40 mg omeprazole (delayed release capsule) administered orally with 240 mL of water QD after an overnight fast of at least 10 hours. On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
|---|---|
|
Age, Continuous
|
36.7 years
STANDARD_DEVIATION 10.18 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9Population: Measured in the Pharmacokinetic Population for the primary endpoint analyses, which included all participants who received both sotorasib, and sotorasib in combination with omeprazole and an acidic beverage, and had evaluable pharmacokinetic data.
Outcome measures
| Measure |
Sotorasib Alone
n=16 Participants
On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
n=14 Participants
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Sotorasib
|
7160 ng/mL
Geometric Coefficient of Variation 22.9
|
4850 ng/mL
Geometric Coefficient of Variation 65.6
|
—
|
PRIMARY outcome
Timeframe: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9Population: Measured in the Pharmacokinetic Population for the primary endpoint analyses, which included all participants who received both sotorasib, and sotorasib in combination with omeprazole and an acidic beverage, and had evaluable pharmacokinetic data.
Outcome measures
| Measure |
Sotorasib Alone
n=16 Participants
On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
n=14 Participants
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sotorasib
|
30200 h*ng/mL
Geometric Coefficient of Variation 33.3
|
23500 h*ng/mL
Geometric Coefficient of Variation 60.4
|
—
|
PRIMARY outcome
Timeframe: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9Population: Measured in the Pharmacokinetic Population for the primary endpoint analyses, which included all participants who received both sotorasib, and sotorasib in combination with omeprazole and an acidic beverage, and had evaluable pharmacokinetic data.
Outcome measures
| Measure |
Sotorasib Alone
n=16 Participants
On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
n=14 Participants
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Sotorasib
|
30000 h*ng/mL
Geometric Coefficient of Variation 33.3
|
23200 h*ng/mL
Geometric Coefficient of Variation 62.2
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 11Population: Measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
An adverse event is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an adverse event that starts during or after the first dose, or starts prior to the first dose and increases in severity after the first dose. Any clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms and vital signs were recorded as an adverse event.
Outcome measures
| Measure |
Sotorasib Alone
n=16 Participants
On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
n=16 Participants
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
n=14 Participants
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
|
0 Participants
|
2 Participants
|
0 Participants
|
Adverse Events
Sotorasib Alone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Omeprazole Alone
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Omeprazole Co-administered With Sotorasib
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 |
Sotorasib Alone
n=16 participants at risk
On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours.
|
Omeprazole Alone
n=16 participants at risk
On Days 4 to 8, participants received 40 mg omeprazole (delayed release capsule) administered orally with 240 mL of water once daily (QD) after an overnight fast of at least 10 hours.
|
Omeprazole Co-administered With Sotorasib
n=14 participants at risk
On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours.
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/16 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
6.2%
1/16 • Number of events 1 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
0.00%
0/14 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
|
Nervous system disorders
Headache
|
0.00%
0/16 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
6.2%
1/16 • Number of events 1 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
0.00%
0/14 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
|
Nervous system disorders
Syncope
|
0.00%
0/16 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
6.2%
1/16 • Number of events 1 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
0.00%
0/14 • Day 1 to Day 11
All-cause mortality, serious and other adverse events were measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
|
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