Brief Title
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
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. Based on the estimated mean ALXN1840 half-life of approximately 2 days in healthy participants (under oral dose of 60 milligrams [mg]), a 14 day period between doses of bupropion is considered sufficient to eliminate, on average, approximately more than 99.2% of the plasma total molybdenum before the next dose of bupropion is administered. The mean elimination half-life (± standard deviation) of bupropion after chronic dosing is 21 (± 9) hours. A 14 day period between doses of bupropion is sufficient to eliminate, on average, more than 99.2% of the plasma bupropion before the next dose of bupropion is administered. The PK profile of ALXN1840 and bupropion will be determined by blood sampling following single dose administration over approximately 5 half-lives or more for both study interventions. Blood sampling for PK assessments will occur at pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, and 336 hours post-dose to ensure full assessment of exposure over time. The nominal 336-hour sample for Period 1 is pre-dose sample for Period 2. In addition to PK sampling, safety and tolerability will be assessed by monitoring adverse events, vital signs, 12-lead electrocardiograms, and laboratory parameters.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum Observed Plasma Concentration (Cmax) Of Bupropion With And Without The Coadministration Of ALXN1840
Secondary Outcome
Cmax Of Hydroxybupropion With And Without The Coadministration Of ALXN1840
Condition
Wilson Disease
Intervention
ALXN1840
Study Arms / Comparison Groups
Treatment A
Description: Participants will receive bupropion.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
38
Start Date
August 2020
Completion Date
April 2021
Primary Completion Date
November 2020
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.
Gender
All
Ages
18 Years - 50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
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Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04526210
Organization ID
ALXN1840-HV-103
Responsible Party
Sponsor
Study Sponsor
Alexion Pharmaceuticals
Study Sponsor
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Verification Date
August 2020