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

Alexion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Wilson Disease

Treatments: Drug: Bupropion Hydrochloride; Drug: ALXN1840

Study type: Interventional

Funder types: Industry

Identifiers

NCT04526210

ALXN1840-HV-103

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

Treatment A

Experimental group

Description:

Participants will receive bupropion.

Treatment:

Drug: Bupropion Hydrochloride

Treatment B

Experimental group

Description:

Participants will receive bupropion with ALXN1840.

Treatment:

Drug: ALXN1840

Drug: Bupropion Hydrochloride