Trial Outcomes & Findings for Phase 1 Study of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants. (NCT NCT04526197)
NCT ID: NCT04526197
Last Updated: 2023-08-21
Results Overview
Blood samples were collected for pharmacokinetics (PK) analysis of celecoxib. Cmax is reported as nanograms (ng)/milliliter (mL).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
Baseline, up to 336 hours post-dose
Results posted on
2023-08-21
Participant Flow
A total of 70 potential participants were screened for this study, and 36 participants were randomized.
Participants were randomized to 1 of 2 treatment sequences (A-B) or (B-A) in a crossover study design during 2 dosing periods. Participants were scheduled to receive either treatment A or B on Day 1 of each dosing period. There was a washout of at least 14 days between the dosing periods.
Participant milestones
| Measure |
Treatment Sequence A-B
All participants were randomized to 1 of 2 treatment sequences (A-B or B-A) and received 1 treatment in each study period; treatment order was defined based on randomization:
* Treatment A: Celecoxib.
* Treatment B: Celecoxib plus ALXN1840.
|
Treatment Sequence B-A
All participants were randomized to 1 of 2 treatment sequences (A-B or B-A) and received 1 treatment in each study period; treatment order was defined based on randomization:
* Treatment A: Celecoxib.
* Treatment B: Celecoxib plus ALXN1840.
|
|---|---|---|
|
Period 1
STARTED
|
18
|
18
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
18
|
18
|
|
Period 1
COMPLETED
|
17
|
17
|
|
Period 1
NOT COMPLETED
|
1
|
1
|
|
Period 2
STARTED
|
17
|
17
|
|
Period 2
Received at Least 1 Dose of Study Drug
|
17
|
17
|
|
Period 2
COMPLETED
|
17
|
15
|
|
Period 2
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Treatment Sequence A-B
All participants were randomized to 1 of 2 treatment sequences (A-B or B-A) and received 1 treatment in each study period; treatment order was defined based on randomization:
* Treatment A: Celecoxib.
* Treatment B: Celecoxib plus ALXN1840.
|
Treatment Sequence B-A
All participants were randomized to 1 of 2 treatment sequences (A-B or B-A) and received 1 treatment in each study period; treatment order was defined based on randomization:
* Treatment A: Celecoxib.
* Treatment B: Celecoxib plus ALXN1840.
|
|---|---|---|
|
Period 1
Adverse Event
|
0
|
1
|
|
Period 1
Withdrawal by Subject
|
1
|
0
|
|
Period 2
Adverse Event
|
0
|
1
|
|
Period 2
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Phase 1 Study of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.
Baseline characteristics by cohort
| Measure |
Treatment Sequence A-B
n=18 Participants
Participants received 1 treatment during each study period in the following sequence:
* Treatment A: Celecoxib.
* Treatment B: Celecoxib plus ALXN1840.
|
Treatment Sequence B-A
n=18 Participants
Participants received 1 treatment during each study period in the following sequence:
* Treatment B: Celecoxib plus ALXN1840.
* Treatment A: Celecoxib.
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
34.5 Years
STANDARD_DEVIATION 8.79 • n=93 Participants
|
33.9 Years
STANDARD_DEVIATION 7.01 • n=4 Participants
|
34.2 Years
STANDARD_DEVIATION 7.84 • n=27 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
4 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
13 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
|
Height
|
170.61 Centimeters
STANDARD_DEVIATION 8.225 • n=93 Participants
|
168.21 Centimeters
STANDARD_DEVIATION 6.997 • n=4 Participants
|
169.41 Centimeters
STANDARD_DEVIATION 7.624 • n=27 Participants
|
|
Weight
|
77.29 Kilograms
STANDARD_DEVIATION 10.466 • n=93 Participants
|
72.06 Kilograms
STANDARD_DEVIATION 9.886 • n=4 Participants
|
74.67 Kilograms
STANDARD_DEVIATION 10.378 • n=27 Participants
|
|
Body Mass Index
|
26.43 Kilograms/squared meter
STANDARD_DEVIATION 1.856 • n=93 Participants
|
25.41 Kilograms/squared meter
STANDARD_DEVIATION 2.596 • n=4 Participants
|
25.92 Kilograms/squared meter
STANDARD_DEVIATION 2.283 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline, up to 336 hours post-dosePopulation: Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data.
Blood samples were collected for pharmacokinetics (PK) analysis of celecoxib. Cmax is reported as nanograms (ng)/milliliter (mL).
Outcome measures
| Measure |
Treatment A
n=35 Participants
Participants who received celecoxib.
|
Treatment B
n=35 Participants
Participants who received celecoxib with ALXN1840.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) Of Celecoxib With And Without The Coadministration Of ALXN1840
|
637.1 ng/mL
Standard Deviation 48.7
|
567.4 ng/mL
Standard Deviation 49.4
|
PRIMARY outcome
Timeframe: Baseline, up to 336 hours post-dosePopulation: Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data.
Blood samples were collected for pharmacokinetic (PK) analysis of celecoxib. Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) is reported as hours•ng/mL (h•ng/mL).
Outcome measures
| Measure |
Treatment A
n=35 Participants
Participants who received celecoxib.
|
Treatment B
n=35 Participants
Participants who received celecoxib with ALXN1840.
|
|---|---|---|
|
Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) Of Celecoxib With And Without The Coadministration Of ALXN1840
|
6406 h•ng/mL
Standard Deviation 40.8
|
6482 h•ng/mL
Standard Deviation 39.9
|
PRIMARY outcome
Timeframe: Baseline, up to 336 hours post-dosePopulation: Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data.
Blood samples were collected for pharmacokinetic (PK) analysis of celecoxib. Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) is reported as h•ng/mL.
Outcome measures
| Measure |
Treatment A
n=35 Participants
Participants who received celecoxib.
|
Treatment B
n=35 Participants
Participants who received celecoxib with ALXN1840.
|
|---|---|---|
|
Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) Of Celecoxib With And Without The Coadministration Of ALXN1840
|
6743 h•ng/mL
Standard Deviation 38
|
6869 h•ng/mL
Standard Deviation 37.8
|
SECONDARY outcome
Timeframe: Baseline, up to 336 hours post-dosePopulation: Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data.
Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and plasma ultrafiltrate (PUF) molybdenum. Cmax is reported as ng/mL.
Outcome measures
| Measure |
Treatment A
n=35 Participants
Participants who received celecoxib.
|
Treatment B
Participants who received celecoxib with ALXN1840.
|
|---|---|---|
|
Cmax Of Molybdenum With Coadministration Of Celecoxib
Total Molybdenum
|
373.4 ng/mL
Standard Deviation 44.8
|
—
|
|
Cmax Of Molybdenum With Coadministration Of Celecoxib
PUF Molybdenum
|
82.44 ng/mL
Standard Deviation 75.5
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to 336 hours post-dosePopulation: Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data.
Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and PUF molybdenum. AUCt is reported as h•ng/mL.
Outcome measures
| Measure |
Treatment A
n=35 Participants
Participants who received celecoxib.
|
Treatment B
Participants who received celecoxib with ALXN1840.
|
|---|---|---|
|
AUCt Of Molybdenum With Coadministration Of Celecoxib
Total Molybdenum
|
19240 h•ng/mL
Standard Deviation 49.1
|
—
|
|
AUCt Of Molybdenum With Coadministration Of Celecoxib
PUF Molybdenum
|
1796 h•ng/mL
Standard Deviation 50.8
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to 336 hours post-dosePopulation: Pharmacokinetic Analysis Set: All randomized participants who received both study drugs and had sufficient plasma samples for evaluable PK data.
Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and PUF molybdenum. AUCinf is reported as h•ng/mL.
Outcome measures
| Measure |
Treatment A
n=35 Participants
Participants who received celecoxib.
|
Treatment B
Participants who received celecoxib with ALXN1840.
|
|---|---|---|
|
AUCinf Of Molybdenum With Coadministration Of Celecoxib
Total Molybdenum
|
20910 h•ng/mL
Standard Deviation 47.3
|
—
|
|
AUCinf Of Molybdenum With Coadministration Of Celecoxib
PUF Molybdenum
|
2305 h•ng/mL
Standard Deviation 36.5
|
—
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Treatment B
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=35 participants at risk
Participants who received celecoxib.
|
Treatment B
n=35 participants at risk
Participants who received celecoxib with ALXN1840.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
5.7%
2/35 • Number of events 2 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Gastrointestinal disorders
Dental discomfort
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
General disorders
Feeling hot
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Injury, poisoning and procedural complications
Limb injury
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Investigations
SARS-CoV-2 test positive
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Nervous system disorders
Dizziness
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Nervous system disorders
Headache
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Reproductive system and breast disorders
Menstruation irregular
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/35 • Day 1 through 15 (± 2) days after final dose of study drug.
|
2.9%
1/35 • Number of events 1 • Day 1 through 15 (± 2) days after final dose of study drug.
|
Additional Information
Alexion Pharmaceuticals, Inc.
Alexion Pharmaceuticals, Inc.
Phone: 855-752-2356
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER