Trial Outcomes & Findings for Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants (NCT NCT05045638)
NCT ID: NCT05045638
Last Updated: 2023-08-14
Results Overview
The pharmacokinetic (PK) parameters were determined using standard non-compartmental methods.
COMPLETED
PHASE1
13 participants
Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6
2023-08-14
Participant Flow
13 participants were enrolled at a single center in the United States between 20 August 2021 and 10 October 2021.
The participants received 10 mg rosuvastatin on Day 1 and 960 mg sotorasib coadministered with 10 mg rosuvastatin on Day 6.
Participant milestones
| Measure |
All Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|
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Overall Study
STARTED
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13
|
|
Overall Study
Received Rosuvastatin Alone
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13
|
|
Overall Study
Received Rosuvastatin Coadministered With Sotorasib
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13
|
|
Overall Study
COMPLETED
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13
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Coadministration of Sotorasib on the Pharmacokinetics of Rosuvastatin in Healthy Participants
Baseline characteristics by cohort
| Measure |
All Participants
n=13 Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|
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Age, Continuous
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41.5 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
|
Sex: Female, Male
Female
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2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
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11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
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3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
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4 Participants
n=5 Participants
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|
Race (NIH/OMB)
White
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9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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0 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, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
The pharmacokinetic (PK) parameters were determined using standard non-compartmental methods.
Outcome measures
| Measure |
Rosuvastatin
n=13 Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
|
Sotorasib + Rosuvastatin
n=13 Participants
On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin
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3.80 ng/mL
Geometric Coefficient of Variation 57.80
|
6.47 ng/mL
Geometric Coefficient of Variation 136.00
|
PRIMARY outcome
Timeframe: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
The PK parameters were determined using standard non-compartmental methods.
Outcome measures
| Measure |
Rosuvastatin
n=13 Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
|
Sotorasib + Rosuvastatin
n=13 Participants
On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|---|
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Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Rosuvastatin
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33.20 h*ng/mL
Geometric Coefficient of Variation 57.00
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44.50 h*ng/mL
Geometric Coefficient of Variation 73.60
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PRIMARY outcome
Timeframe: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
The PK parameters were determined using standard non-compartmental methods.
Outcome measures
| Measure |
Rosuvastatin
n=12 Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
|
Sotorasib + Rosuvastatin
n=11 Participants
On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|---|
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AUC From Time Zero to Infinity (AUCinf) of Rosuvastatin
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36.20 h*ng/mL
Geometric Coefficient of Variation 60.10
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48.40 h*ng/mL
Geometric Coefficient of Variation 78.90
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SECONDARY outcome
Timeframe: Day 1 to Day 41Population: The safety population included all participants who received at least 1 dose of sotorasib or rosuvastatin and had at least 1 postdose safety assessment.
Any clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms (ECGs), and vital signs results were recorded as AEs.
Outcome measures
| Measure |
Rosuvastatin
n=13 Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
|
Sotorasib + Rosuvastatin
n=13 Participants
On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|---|
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Number of Participants Reporting Any Treatment-Emergent Adverse Events (TEAEs)
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0 Participants
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0 Participants
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SECONDARY outcome
Timeframe: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
The PK parameters were determined using standard non-compartmental methods.
Outcome measures
| Measure |
Rosuvastatin
n=13 Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
|
Sotorasib + Rosuvastatin
On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|---|
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Cmax of Sotorasib
|
4650 ng/mL
Geometric Coefficient of Variation 86.2
|
—
|
SECONDARY outcome
Timeframe: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
The PK parameters were determined using standard non-compartmental methods.
Outcome measures
| Measure |
Rosuvastatin
n=13 Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
|
Sotorasib + Rosuvastatin
On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|---|
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AUClast of Sotorasib
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22500 h*ng/mL
Geometric Coefficient of Variation 74.3
|
—
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SECONDARY outcome
Timeframe: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
The PK parameters were determined using standard non-compartmental methods.
Outcome measures
| Measure |
Rosuvastatin
n=13 Participants
On Day 1, rosuvastatin was administered as a single 10 mg dose. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
|
Sotorasib + Rosuvastatin
On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose.
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|---|---|---|
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AUCinf of Sotorasib
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22900 h*ng/mL
Geometric Coefficient of Variation 71.7
|
—
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Adverse Events
Rosuvastatin
Sotorasib + Rosuvastatin
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
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