Clinical trial NCT04526197: Phase 1 Study of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.
Official title: A Phase 1, Randomized, 2-Period, 2-Sequence, Cross-over Study to Determine the Effect of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Wilson Disease
Keywords: Cytochrome P450
Healthy
ALXN1840
Celecoxib
CYP2C9
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants were randomized to 1 of 2 treatment sequences: A-B or B-A.
Primary purpose: TREATMENT

Brief summary: This was a Phase 1, randomized, 2-period, 2-sequence, cross-over study designed to determine the effect of ALXN1840 on the metabolism of celecoxib, a sensitive cytochrome P450 2C9 (CYP2C9) substrate, in healthy male and female participants. The safety and tolerability of ALXN1840 were determined along with ALXN1840 pharmacokinetics (PK) in plasma as measured via total molybdenum with the coadministration of celecoxib.

Detailed description: The study was conducted as a randomized, 2-period, 2-sequence, cross-over study to determine the effect of a single dose of ALXN1840 (perpetrator) on the single-dose celecoxib (victim) kinetics in healthy male and female participants.

The study had a Screening period (Day -28 to Day -2), two 11-day study periods (Day 1 to Day 11) with a minimum of 14 days between doses of celecoxib, and an End of Study Visit (Day 15 ± 2 days) after Period 2 dosing. Participants only reported to the clinical research unit (CRU) on the day prior to the first dose because they were kept in the CRU during the wash-out period due to coronavirus disease 2019.

All participants received a single dose of celecoxib alone (Treatment A) and celecoxib coadministered with ALXN1840 (Treatment B) during the study, 1 in each treatment period. Based on randomization, participants were administered either Treatments A-B or Treatments B-A in each study period.

The PK profile of ALXN1840 and celecoxib was determined by blood sampling following single-dose administration. In addition to PK sampling, safety and tolerability were assessed by monitoring adverse events, vital signs, 12-lead electrocardiograms, physical examinations, and laboratory parameters.

Eligibility criteria: Inclusion Criteria:

* Adequate venous access in the left or right arm to allow the collection of blood samples.
* Bodyweight ≥ 45 to ≤ 100 kilograms (kg) and body mass index within the range of 18 to \< 30 kg/meter squared.
* Willing and able to follow protocol-specified contraception requirements.
* Capable of giving signed informed consent.

Exclusion Criteria:

* History or presence of/significant medical history.
* Clinically significant multiple or severe allergies.
* Lymphoma, leukemia, or any malignancy within 5 years.
* Breast cancer within the past 10 years.
* Serum creatinine \> upper limit of normal (ULN) of the reference range.
* Alanine aminotransferase, aspartate aminotransferase, or total bilirubin \> ULN.
* Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* QTc \> 450 milliseconds (msec) for male participants or \> 470 msec for female participants.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) Of Celecoxib With And Without The Coadministration Of ALXN1840
timeFrame: Baseline, up to 336 hours post-dose
measure: 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
timeFrame: Baseline, up to 336 hours post-dose
measure: Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) Of Celecoxib With And Without The Coadministration Of ALXN1840
timeFrame: Baseline, up to 336 hours post-dose
Secondary outcomes:
measure: Cmax Of Molybdenum With Coadministration Of Celecoxib
timeFrame: Baseline, up to 336 hours post-dose
measure: AUCt Of Molybdenum With Coadministration Of Celecoxib
timeFrame: Baseline, up to 336 hours post-dose
measure: AUCinf Of Molybdenum With Coadministration Of Celecoxib
timeFrame: Baseline, up to 336 hours post-dose
Other outcomes:
Locations:
city: Austin
country: United States
facility: Clinical Trial Site
state: Texas
Study officials:
References: