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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
ALXN1840 will be administered orally as a single dose as 4 x 15 mg enteric-coated tablets with 240 milliliters of water (fasting), for a total dose of 60 mg.
Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting).
Clinical Trial Site
Austin, Texas, United States
Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
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
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUCinf) of Bupropion With and Without the Coadministration of ALXN1840
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
Cmax of Plasma Total Molybdenum With Coadministration of Bupropion
Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only.
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
AUCt of Plasma Total Molybdenum With Coadministration of Bupropion
Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only.
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Time frame: Pre-dose (Day 1) up to 336 hours post-dose
AUCinf of Plasma Total Molybdenum With Coadministration of Bupropion
Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only.
Time frame: Pre-dose (Day 1) up to 336 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with the study drug and which did not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A TEAE was defined as any AE that began or worsened on or after the first dose of treatment until the end of study (EOS) or early termination (ET). An AE that occurred during the washout period between drugs was considered treatment emergent to the last drug given. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Day 1 up to Day 15