Study of ALXN1840 on the Metabolism of a CYP2B6 Substrate in Healthy Participants

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Wilson Disease

Intervention / Treatment
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* Drug: ALXN1840
* Drug: Bupropion Hydrochloride


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Participants will receive bupropion. | Drug: Bupropion Hydrochloride<br>* Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting).<br>* Other names: Wellbutrin SR 150;|
| Experimental: Treatment B<br>Participants will receive bupropion with ALXN1840. | Drug: ALXN1840<br>* 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.<br>* Other names: Tiomolibdate choline;Drug: Bupropion Hydrochloride<br>* Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting).<br>* Other names: Wellbutrin SR 150;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840 |  | 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 |  | 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 |  | Pre-dose (Day 1) up to 336 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840 |  | Pre-dose (Day 1) up to 336 hours post-dose | 
| AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840 |  | Pre-dose (Day 1) up to 336 hours post-dose | 
| AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840 |  | 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. | 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. | 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. | 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. | Day 1 up to Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytochrome P450, Healthy, ALXN1840