Trial Outcomes & Findings for Study of the Effect of Food and a Proton Pump Inhibitor (PPI; Omeprazole) on LOXO-305 in Healthy Participants (NCT NCT05134350)
NCT ID: NCT05134350
Last Updated: 2025-01-10
Results Overview
PK: AUC(0-24) hours of LOXO-305 is reported. AUC(0-24) was calculated by the linear trapezoidal method.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
10 participants
Primary outcome timeframe
Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post LOXO-305 dose
Results posted on
2025-01-10
Participant Flow
Participants were randomized to 2 treatment sequences (ABC and BAC), with each sequence having 3 periods where participants were crossed over between the periods in each sequence. A washout period of 7 days was maintained between each treatment period.
Participant milestones
| Measure |
Treatment Sequence 1: ABC
* Period 1: Single oral dose of 200 milligram (mg) LOXO-305 (Fasted state) on Day 1 (Treatment A)
* Period 2: Single oral dose of 200 mg LOXO-305 (Fed state) on Day 8 (Treatment B)
* Period 3: Single oral dose of 40 mg Omeprazole (Fasted state) on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole (Fasted state) on Day 18 (Treatment C)
A washout period of 7 days was maintained between each treatment period.
|
Treatment Sequence 2: BAC
* Period 1: Single oral dose of 200 mg LOXO-305 (Fed state) on Day 1 (Treatment B)
* Period 2: Single oral dose of 200 mg LOXO-305 (Fasted state) on Day 8 (Treatment A)
* Period 3: Single oral dose of 40 mg Omeprazole (Fasted state) on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole (Fasted state) on Day 18 (Treatment C)
A washout period of 7 days was maintained between each treatment period.
|
|---|---|---|
|
Period 1
STARTED
|
5
|
5
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
5
|
5
|
|
Period 1
COMPLETED
|
5
|
5
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
5
|
5
|
|
Period 2
COMPLETED
|
5
|
5
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
|
Period 3
STARTED
|
5
|
5
|
|
Period 3
COMPLETED
|
5
|
5
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of the Effect of Food and a Proton Pump Inhibitor (PPI; Omeprazole) on LOXO-305 in Healthy Participants
Baseline characteristics by cohort
| Measure |
Treatment Sequence 1: ABC
n=5 Participants
* Period 1: Single oral dose of 200 mg LOXO-305 (Fasted state) on Day 1 (Treatment A)
* Period 2: Single oral dose of 200 mg LOXO-305 (Fed state) on Day 8 (Treatment B)
* Period 3: Single oral dose of 40 mg Omeprazole (Fasted state) on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole (Fasted state) on Day 18 (Treatment C)
A washout period of 7 days was maintained between each treatment period.
|
Treatment Sequence 2: BAC
n=5 Participants
* Period 1: Single oral dose of 200 mg LOXO-305 (Fed state) on Day 1 (Treatment B)
* Period 2: Single oral dose of 200 mg LOXO-305 (Fasted state) on Day 8 (Treatment A)
* Period 3: Single oral dose of 40 mg Omeprazole (Fasted state) on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole (Fasted state) on Day 18 (Treatment C)
A washout period of 7 days was maintained between each treatment period.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.2 years
STANDARD_DEVIATION 10.66 • n=5 Participants
|
35.2 years
STANDARD_DEVIATION 4.87 • n=7 Participants
|
39.2 years
STANDARD_DEVIATION 8.88 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 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 (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post LOXO-305 dosePopulation: All participants who received at least one dose of LOXO-305 and had evaluable PK data.
PK: AUC(0-24) hours of LOXO-305 is reported. AUC(0-24) was calculated by the linear trapezoidal method.
Outcome measures
| Measure |
Treatment A: 200 mg LOXO-305 (Fasted)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 Participants
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
|---|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration-time Curve From Hour 0 to 24 (AUC [0-24]) Hours of LOXO-305
|
55100 hour*nanograms per milliliter
Geometric Coefficient of Variation 17.5
|
51900 hour*nanograms per milliliter
Geometric Coefficient of Variation 12.8
|
59900 hour*nanograms per milliliter
Geometric Coefficient of Variation 15.5
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePopulation: All participants who received at least one dose of LOXO-305 and had evaluable PK data.
PK: AUC(0-t) of LOXO-305 is reported. AUC(0-t) was calculated by linear trapezoidal method.
Outcome measures
| Measure |
Treatment A: 200 mg LOXO-305 (Fasted)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 Participants
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
|---|---|---|---|
|
PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of LOXO-305
|
89400 hour*nanograms per milliliter
Geometric Coefficient of Variation 17.8
|
85100 hour*nanograms per milliliter
Geometric Coefficient of Variation 19.3
|
99600 hour*nanograms per milliliter
Geometric Coefficient of Variation 17.1
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePopulation: All participants who received at least one dose of LOXO-305 and had evaluable PK data.
PK: AUC(0-inf) of LOXO-305 is reported. AUC(0-inf) was calculated using the formula: AUC(0-inf) = AUC(0-t) + Ct/λZ; where Ct is the last measurable concentration and λZ is the apparent terminal elimination rate constant.
Outcome measures
| Measure |
Treatment A: 200 mg LOXO-305 (Fasted)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 Participants
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
|---|---|---|---|
|
PK: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC[0-Inf]) of LOXO-305
|
90200 hour*nanograms per milliliter
Geometric Coefficient of Variation 17.6
|
86100 hour*nanograms per milliliter
Geometric Coefficient of Variation 18.9
|
101000 hour*nanograms per milliliter
Geometric Coefficient of Variation 16.8
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePopulation: All participants who received at least one dose of LOXO-305 and had evaluable PK data.
PK: %AUCextrap of LOXO-305 is reported.
Outcome measures
| Measure |
Treatment A: 200 mg LOXO-305 (Fasted)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 Participants
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
|---|---|---|---|
|
PK: Percentage Extrapolation for AUC0-Inf (%AUCextrap) of LOXO-305
|
0.911 percentage of extrapolation
Geometric Coefficient of Variation 27.2
|
1.12 percentage of extrapolation
Geometric Coefficient of Variation 42.6
|
0.893 percentage of extrapolation
Geometric Coefficient of Variation 34.5
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePopulation: All participants who received at least one dose of LOXO-305 and had evaluable PK data.
PK: Cmax of LOXO-305 is reported.
Outcome measures
| Measure |
Treatment A: 200 mg LOXO-305 (Fasted)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 Participants
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
|---|---|---|---|
|
PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305
|
5450 nanograms per milliliter
Geometric Coefficient of Variation 31.7
|
4340 nanograms per milliliter
Geometric Coefficient of Variation 16.6
|
5490 nanograms per milliliter
Geometric Coefficient of Variation 16.7
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePopulation: All participants who received at least one dose of LOXO-305 and had evaluable PK data.
PK: tmax of LOXO-305 is reported.
Outcome measures
| Measure |
Treatment A: 200 mg LOXO-305 (Fasted)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 Participants
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
|---|---|---|---|
|
PK: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-305
|
2.50 hours
Interval 1.5 to 4.0
|
3.00 hours
Interval 1.0 to 4.0
|
2.25 hours
Interval 1.5 to 3.0
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePopulation: All participants who received at least one dose of LOXO-305 and had evaluable PK data.
PK: t½ of LOXO-305 is reported.
Outcome measures
| Measure |
Treatment A: 200 mg LOXO-305 (Fasted)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 Participants
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
|---|---|---|---|
|
PK: Apparent Terminal Elimination Half-life (t½) of LOXO-305
|
20.2 hours
Standard Deviation 4.24
|
21.5 hours
Standard Deviation 5.75
|
19.7 hours
Standard Deviation 2.87
|
PRIMARY outcome
Timeframe: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePopulation: All participants who received at least one dose of LOXO-305 and had evaluable PK data.
PK: CL/F of LOXO-305 is reported.
Outcome measures
| Measure |
Treatment A: 200 mg LOXO-305 (Fasted)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 Participants
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 Participants
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
|---|---|---|---|
|
PK: Apparent Systemic Clearance (CL/F) of LOXO-305
|
2.22 Liter per Hours (L/h)
Geometric Coefficient of Variation 17.6
|
2.32 Liter per Hours (L/h)
Geometric Coefficient of Variation 18.9
|
1.99 Liter per Hours (L/h)
Geometric Coefficient of Variation 16.8
|
Adverse Events
Treatment A: 200 mg LOXO-305 (Fasted)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Treatment B: 200 mg LOXO-305 (Fed)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Treatment C: 40 mg Omeprazole (Fasted)
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: 200 mg LOXO-305 (Fasted)
n=10 participants at risk
All the participants who received single oral dose of 200 mg LOXO-305 in fasted state on Day 1 (sequence 1), Day 8 (sequence 2).
|
Treatment B: 200 mg LOXO-305 (Fed)
n=10 participants at risk
All the participants who received single oral dose of 200 mg LOXO-305 in fed state on Day 1 (sequence 2), Day 8 (sequence 1).
|
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)
n=10 participants at risk
All participants in sequence 1 and 2 who received single oral dose of 40 mg Omeprazole in fasted state on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole in fasted state on Day 18.
|
Treatment C: 40 mg Omeprazole (Fasted)
n=10 participants at risk
All participants who received single oral dose of 40 mg Omeprazole (Fasted) on Day 15 to 17.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
10.0%
1/10 • Number of events 1 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
10.0%
1/10 • Number of events 1 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
10.0%
1/10 • Number of events 1 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
0.00%
0/10 • Day 1 up to Day 32
All participants who received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60