Clinical trial NCT04526210: Study of ALXN1840 on the Metabolism of a CYP2B6 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 CYP2B6 Substrate in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Wilson Disease
Keywords: Cytochrome P450
Healthy
ALXN1840
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-25
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, randomized, 2-period, 2-sequence, cross-over study designed to determine the effect of ALXN1840 on the metabolism of bupropion, a sensitive cytochrome P450 2B6 (CYP2B6) substrate, in healthy male and female participants. The safety and tolerability of ALXN1840 will be determined along with ALXN1840 pharmacokinetics (PK) in plasma as measured via total molybdenum with the coadministration of bupropion.

Detailed description: The study is being 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 bupropion (victim) kinetics in healthy male and female participants.

The study has 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 bupropion, and an End of Study Visit (Day 15 ± 2 days) after Period 2 dosing. Participants will report to the clinical research unit on the day prior (Day -1) to both dosing periods. All participants will receive 1 treatment in each study period; treatment order will be defined based on randomization: Treatments A and B.

The time between dosing bupropion alone or in combination with ALXN1840 in each treatment sequence will be a minimum of 14 days.

The PK profile of ALXN1840 and bupropion will be determined by blood sampling following single dose administration.

Eligibility criteria: Inclusion Criteria:

* Adequate venous access in the left or right arm to allow the collection of blood samples.
* Body weight ≥ 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 Bupropion With and Without the Coadministration of ALXN1840
timeFrame: Pre-dose (Day 1) 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 Bupropion With and Without the Coadministration of ALXN1840
timeFrame: Pre-dose (Day 1) up to 336 hours post-dose
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUCinf) of Bupropion With and Without the Coadministration of ALXN1840
timeFrame: Pre-dose (Day 1) up to 336 hours post-dose
Secondary outcomes:
measure: Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840
timeFrame: Pre-dose (Day 1) up to 336 hours post-dose
measure: AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840
timeFrame: Pre-dose (Day 1) up to 336 hours post-dose
measure: AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840
timeFrame: Pre-dose (Day 1) up to 336 hours post-dose
measure: Cmax of Plasma Total Molybdenum With Coadministration of Bupropion
timeFrame: Pre-dose (Day 1) up to 336 hours post-dose
measure: AUCt of Plasma Total Molybdenum With Coadministration of Bupropion
timeFrame: Pre-dose (Day 1) up to 336 hours post-dose
measure: AUCinf of Plasma Total Molybdenum With Coadministration of Bupropion
timeFrame: Pre-dose (Day 1) up to 336 hours post-dose
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Day 15
Other outcomes:
Locations:
city: Austin
country: United States
facility: Clinical Trial Site
state: Texas
Study officials:
References: