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

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

Sponsors

Lead Sponsor: Alexion Pharmaceuticals

Source Alexion Pharmaceuticals
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.

Overall Status Enrolling by invitation
Start Date August 2020
Completion Date April 2021
Primary Completion Date November 2020
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Maximum Observed Plasma Concentration (Cmax) Of Bupropion With And Without The Coadministration Of ALXN1840 Baseline, 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 Baseline, 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 Baseline, up to 336 hours post-dose
Secondary Outcome
Measure Time Frame
Cmax Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 Baseline, up to 336 hours post-dose
AUCt Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 Baseline, up to 336 hours post-dose
AUCinf Of Hydroxybupropion With And Without The Coadministration Of ALXN1840 Baseline, up to 336 hours post-dose
Cmax Of Molybdenum With Coadministration Of Bupropion Baseline, up to 336 hours post-dose
AUCt Of Molybdenum With Coadministration Of Bupropion Baseline, up to 336 hours post-dose
AUCinf Of Molybdenum With Coadministration Of Bupropion Baseline, up to 336 hours post-dose
Enrollment 38
Condition
Intervention

Intervention Type: Drug

Intervention Name: ALXN1840

Description: 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.

Arm Group Label: Treatment B

Intervention Type: Drug

Intervention Name: Bupropion Hydrochloride

Description: Bupropion hydrochloride will be administered orally as a single dose as one 150 mg tablet with 240 milliliters of water (fasting).

Other Name: Wellbutrin SR 150

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

Minimum Age: 18 Years

Maximum Age: 50 Years

Healthy Volunteers: Accepts Healthy Volunteers

Location
Facility: Clinical Trial Site
Location Countries

United States

Verification Date

August 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Treatment A

Type: Experimental

Description: Participants will receive bupropion.

Label: Treatment B

Type: Experimental

Description: Participants will receive bupropion with ALXN1840.

Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov