Wilson DiseasePhase 1NCT04526197
Phase 1 Study of ALXN1840 on the Metabolism of a CYP2C9 Substrate in Healthy Participants.
A Phase 1 study testing ALXN1840 and Celecoxib in people with Wilson Disease, run by Alexion Pharmaceuticals, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Wilson Disease
- What is being tested?
- ALXN1840 and Celecoxib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jul 2020to 3 Nov 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- Wilson Disease
- Being tested
- ALXN1840, Celecoxib
- Keywords
- Cytochrome P450, Healthy, ALXN1840, Celecoxib, CYP2C9
- Medical subject headings
- Hepatolenticular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALXN1840Drug
Also called WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate choline
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.
CelecoxibDrug
Celecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting).
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence A-B | Experimental | Participants received 1 treatment during each study period in the following sequence:
* Treatment A: Celecoxib.
* Treatment B: Celecoxib plus ALXN1840. Receives: Drug: ALXN1840; Drug: Celecoxib |
| Treatment Sequence B-A | Experimental | Participants received 1 treatment during each study period in the following sequence:
* Treatment B: Celecoxib plus ALXN1840.
* Treatment A: Celecoxib. Receives: Drug: ALXN1840; Drug: Celecoxib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax) Of Celecoxib With And Without The Coadministration Of ALXN1840
Blood samples were collected for pharmacokinetics (PK) analysis of celecoxib. Cmax is reported as nanograms (ng)/milliliter (mL).
Measured: 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
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).
Measured: 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
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.
Measured: Baseline, up to 336 hours post-dose
Secondary outcomes (3)
Cmax Of Molybdenum With Coadministration Of Celecoxib
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.
Measured: Baseline, up to 336 hours post-dose
AUCt Of Molybdenum With Coadministration Of Celecoxib
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.
Measured: Baseline, up to 336 hours post-dose
AUCinf Of Molybdenum With Coadministration Of Celecoxib
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.
Measured: Baseline, up to 336 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2020
- Study start7 Jul 2020
- Primary completion3 Nov 2020
- Study completion3 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Wilson DiseaseStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants were randomized to 1 of 2 treatment sequences: A-B or B-A.
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04526197
- Sponsor's protocol ID
- ALXN1840-HV-105
- Status last verified
- Oct 2022
- First submitted
- 19 Aug 2020
- Last updated
- 21 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04526197
- Acronym / sponsor ID
- ALXN1840-HV-105
- Conditions
- Wilson Disease
- Keywords
- Cytochrome P450, Healthy, ALXN1840, Celecoxib, CYP2C9
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Jul 2020 (actual)
- Primary completion
- 3 Nov 2020 (actual)
- Study completion
- 3 Nov 2020 (actual)
- First posted
- 25 Aug 2020 (actual)
- Results
- Posted 21 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants were randomized to 1 of 2 treatment sequences: A-B or B-A.
| Arm | Type | Receives |
|---|---|---|
| Treatment Sequence A-B | Experimental | Drug: ALXN1840, Drug: CelecoxibParticipants received 1 treatment during each study period in the following sequence: * Treatment A: Celecoxib. * Treatment B: Celecoxib plus ALXN1840. |
| Treatment Sequence B-A | Experimental | Drug: ALXN1840, Drug: CelecoxibParticipants received 1 treatment during each study period in the following sequence: * Treatment B: Celecoxib plus ALXN1840. * Treatment A: Celecoxib. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALXN1840Also: WTX101, Bis-choline tetrathiomolybdate, Tiomolibdate cholineALXN1840 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. | Drug | Treatment Sequence A-B, Treatment Sequence B-A |
| CelecoxibCelecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting). | Drug | Treatment Sequence A-B, Treatment Sequence B-A |
Primary outcome
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).
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).
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.
3 secondary outcomes
Cmax Of Molybdenum With Coadministration Of Celecoxib
Time frame: Baseline, up to 336 hours post-dose
AUCt Of Molybdenum With Coadministration Of Celecoxib
Time frame: Baseline, up to 336 hours post-dose
AUCinf Of Molybdenum With Coadministration Of Celecoxib
Time frame: Baseline, up to 336 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALXN1840 and Celecoxib in people with Wilson Disease, run by Alexion Pharmaceuticals, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Observed Plasma Concentration (Cmax) Of Celecoxib With And Without The Coadministration Of ALXN1840 (time frame: Baseline, up to 336 hours post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.