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

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT04526197

Collaborator

(none)

Enrollment

Location

Arms

3.9

Actual Duration (Months)

9.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Wilson Disease	Drug: ALXN1840 Drug: Celecoxib	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Participants were randomized to 1 of 2 treatment sequences: A-B or B-A.Participants were randomized to 1 of 2 treatment sequences: A-B or B-A.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Jul 8, 2020

Actual Primary Completion Date :

Nov 3, 2020

Actual Study Completion Date :

Nov 3, 2020

Arms and Interventions

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: WTX101 Bis-choline tetrathiomolybdate Tiomolibdate choline 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: WTX101 Bis-choline tetrathiomolybdate Tiomolibdate choline Drug: Celecoxib Celecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting).

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:

WTX101

Bis-choline tetrathiomolybdate

Tiomolibdate choline

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:

WTX101

Bis-choline tetrathiomolybdate

Tiomolibdate choline

Drug: Celecoxib

Celecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting).

Outcome Measures

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) Of Celecoxib 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 Celecoxib 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 Celecoxib With And Without The Coadministration Of ALXN1840 [Baseline, up to 336 hours post-dose]

Secondary Outcome Measures

Cmax Of Molybdenum With Coadministration Of Celecoxib [Baseline, up to 336 hours post-dose]
AUCt Of Molybdenum With Coadministration Of Celecoxib [Baseline, up to 336 hours post-dose]
AUCinf Of Molybdenum With Coadministration Of Celecoxib [Baseline, up to 336 hours post-dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.