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

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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

, , 


Verification Date

August 2020