Phase 1 Study of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.

October 18, 2022 updated by: Alexion

A Phase 1, Randomized, 2-Period, 2-Sequence, Cross-over Study to Determine the Effect of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.

This was a Phase 1, randomized, 2-period, 2-sequence, cross-over study designed to determine the effect of ALXN1840 on the metabolism of celecoxib, a sensitive cytochrome P450 2C9 (CYP2C9) substrate, in healthy male and female participants. The safety and tolerability of ALXN1840 were determined along with ALXN1840 pharmacokinetics (PK) in plasma as measured via total molybdenum with the coadministration of celecoxib.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study was 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 celecoxib (victim) kinetics in healthy male and female participants.

The study had 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 celecoxib, and an End of Study Visit (Day 15 ± 2 days) after Period 2 dosing. Participants only reported to the clinical research unit (CRU) on the day prior to the first dose because they were kept in the CRU during the wash-out period due to coronavirus disease 2019.

All participants received a single dose of celecoxib alone (Treatment A) and celecoxib coadministered with ALXN1840 (Treatment B) during the study, 1 in each treatment period. Based on randomization, participants were administered either Treatments A-B or Treatments B-A in each study period.

The PK profile of ALXN1840 and celecoxib was determined by blood sampling following single-dose administration. In addition to PK sampling, safety and tolerability were assessed by monitoring adverse events, vital signs, 12-lead electrocardiograms, physical examinations, and laboratory parameters.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Austin, Texas, United States, 78744
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 48 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Adequate venous access in the left or right arm to allow the collection of blood samples.
  • Bodyweight ≥ 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Sequence A-B

Participants received 1 treatment during each study period in the following sequence:

  • Treatment A: Celecoxib.
  • Treatment B: Celecoxib plus ALXN1840.
Drug: ALXN1840
ALXN1840 was administered orally as a single dose as 4 x 15 milligram (mg) enteric-coated tablets with 240 milliliters (mL) of water (fasting), for a total dose of 60 mg.
Other Names:
  • Tiomolibdate choline
  • WTX101
  • Bis-choline tetrathiomolybdate
Drug: Celecoxib
Celecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting).
Experimental: Treatment Sequence B-A

Participants received 1 treatment during each study period in the following sequence:

  • Treatment B: Celecoxib plus ALXN1840.
  • Treatment A: Celecoxib.
Drug: ALXN1840
ALXN1840 was administered orally as a single dose as 4 x 15 milligram (mg) enteric-coated tablets with 240 milliliters (mL) of water (fasting), for a total dose of 60 mg.
Other Names:
  • Tiomolibdate choline
  • WTX101
  • Bis-choline tetrathiomolybdate
Drug: Celecoxib
Celecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax) Of Celecoxib With And Without The Coadministration Of ALXN1840
Time Frame: Baseline, up to 336 hours post-dose
Blood samples were collected for pharmacokinetics (PK) analysis of celecoxib. Cmax is reported as nanograms (ng)/milliliter (mL).
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 Celecoxib With And Without The Coadministration Of ALXN1840
Time Frame: Baseline, up to 336 hours post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of celecoxib. Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) is reported as hours•ng/mL (h•ng/mL).
Baseline, up to 336 hours post-dose
Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) Of Celecoxib With And Without The Coadministration Of ALXN1840
Time Frame: Baseline, up to 336 hours post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of celecoxib. Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) is reported as h•ng/mL.
Baseline, up to 336 hours post-dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax Of Molybdenum With Coadministration Of Celecoxib
Time Frame: Baseline, up to 336 hours post-dose
Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and plasma ultrafiltrate (PUF) molybdenum. Cmax is reported as ng/mL.
Baseline, up to 336 hours post-dose
AUCt Of Molybdenum With Coadministration Of Celecoxib
Time Frame: Baseline, up to 336 hours post-dose
Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and PUF molybdenum. AUCt is reported as h•ng/mL.
Baseline, up to 336 hours post-dose
AUCinf Of Molybdenum With Coadministration Of Celecoxib
Time Frame: Baseline, up to 336 hours post-dose
Blood samples were collected for PK analysis of total molybdenum (as a measure of ALXN1840) and PUF molybdenum. AUCinf is reported as h•ng/mL.
Baseline, up to 336 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 7, 2020

Primary Completion (Actual)

November 3, 2020

Study Completion (Actual)

November 3, 2020

Study Registration Dates

First Submitted

August 19, 2020

First Submitted That Met QC Criteria

August 21, 2020

First Posted (Actual)

August 25, 2020

Study Record Updates

Last Update Posted (Actual)

August 21, 2023

Last Update Submitted That Met QC Criteria

October 18, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALXN1840-HV-105

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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