Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ALXN1840 · 10 trials · 2 indications
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Copper balance is defined as the difference between the measured copper input in food and drink, and the measured copper elimination in urine and feces, and was calculated as the average daily copper balance over the collection period.
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8 to 2.3 micromole \[μmol\]l/liter \[L\]\]) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of copper (Cu) bound to ceruloplasmin (CP) from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Descriptive statistics are reported.
Whole blood samples were collected for the measurement of plasma concentrations of total Mo via inductively coupled plasma-mass spectroscopy (ICP-MS).
Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS.
Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS.
Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS.
Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS.
Twelve-lead electrocardiograms (ECGs) were extracted from approximately 25-hour continuous (Holter) recordings on Day -1 of Treatment Period 1 and Days 1 and 2 in each treatment period. Change from baseline in the QT interval was corrected for heart rate using Fridericia's formula (ΔQTcF). ΔQTcF was based on a mixed-effects model for repeated measures (MMRM) with ΔQTcF as the dependent variable; period, sequence, time, treatment, and time-by-treatment interaction as fixed effects; and baseline QTc and sex as covariates. ΔΔQTc = LS mean ΔQTcF after ALXN1840 dosing minus LS mean ΔQTcF after placebo. If the upper bound of the confidence interval (CI) of ΔΔQTcF was \< 10 ms for all postdose time points, ALXN1840 was concluded to not have a significant effect on QT interval prolongation.
Blood samples were collected for pharmacokinetics (PK) analysis of celecoxib. Cmax is reported as nanograms (ng)/milliliter (mL).
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).
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.
Copper balance was defined as the difference in copper input and copper output. A negative copper balance indicated greater copper output than copper intake. Copper input was defined as the sum of all copper input as measured in all food and fluids over the specified period. Copper output was defined as the sum of all copper output as measured in urine and feces over the specified collection period. Baseline was defined as the average of the nonmissing values on or before first study drug administration from Day -4 to Day -1.
The pharmacokinetic (PK) data of plasma total molybdenum were analyzed in the scope of this study as a surrogate measure for ALXN1840. Whole blood samples were collected for the measurement of plasma concentrations of total molybdenum via inductively coupled plasma-mass spectroscopy (ICP-MS).
The PK data of plasma total molybdenum were analyzed in the scope of this study as a surrogate measure for ALXN1840. Whole blood samples were collected for the measurement of plasma concentrations of total molybdenum via ICP-MS.
AUC0-t was calculated by the linear trapezoidal method.
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with the study drug and which did not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A TEAE was defined as an AE that started or worsened at the time of or after study drug administration. An AE that occurred during the washout period between drugs was considered treatment emergent to the last drug given. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
| Arm | Type | Description |
|---|---|---|
| ALXN1840 | EXPERIMENTAL | Participants will be administered ALXN1840 at a dose of 15 milligrams (mg)/day on Day 1 through Day 28 and then increased to 30 mg/day on Day 29 through Day 39 |
| Crossover ALXN1840 Sequence 1 | EXPERIMENTAL | Participants will first receive a single dose of ALXN1840 test formulation on Day 1 of Period 1. After a washout period of 14 days, they will then receive a single dose of ALXN1840 reference formulation on Day 1 of Period 2. |
| Crossover ALXN1840 Sequence 2 | EXPERIMENTAL | Participants will first receive a single dose of ALXN1840 reference formulation on Day 1 of Period 1. After a washout period of 14 days, they will then receive a single dose of ALXN1840 test formulation on Day 1 of Period 2. |
| Parallel Dose-proportionality Extension: ALXN1840 Dose 1 | EXPERIMENTAL | Participants will receive a single dose of ALXN1840. |
| Parallel Dose-proportionality Extension: ALXN1840 Dose 2 | EXPERIMENTAL | Participants will receive a single dose of ALXN1840. |
| Parallel Dose-proportionality Extension: ALXN1840 Dose 3 | EXPERIMENTAL | Participants will receive a single dose of ALXN1840. |
| Parallel Dose-proportionality Extension: ALXN1840 Dose 4 | EXPERIMENTAL | Participants will receive a single dose of ALXN1840. |
| Treatment A | EXPERIMENTAL | Participants will receive bupropion. |
| Treatment B | EXPERIMENTAL | Participants will receive bupropion with ALXN1840. |
| Treatment Sequence 1 | EXPERIMENTAL | On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: ALXN1840. Period 2: Placebo-matching ALXN1840. Period 3: Moxifloxacin. |
| Treatment Sequence 2 | EXPERIMENTAL | On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: ALXN1840. Period 2: Moxifloxacin. Period 3: Placebo-matching ALXN1840. |
| Treatment Sequence 3 | EXPERIMENTAL | On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: Placebo-matching ALXN1840. Period 2: ALXN1840. Period 3: Moxifloxacin. |
| Treatment Sequence 4 | EXPERIMENTAL | On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: Placebo-matching ALXN1840. Period 2: Moxifloxacin. Period 3: ALXN1840. |
| Treatment Sequence 5 | EXPERIMENTAL | On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: Moxifloxacin. Period 2: ALXN1840. Period 3: Placebo-matching ALXN1840. |
| Treatment Sequence 6 | EXPERIMENTAL | On Day 1 of each period, participants will receive a single dose of the following study interventions: Period 1: Moxifloxacin. Period 2: Placebo-matching ALXN1840. Period 3: ALXN1840. |
| 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. |
| 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. |
| Sequence 1 (AB) | EXPERIMENTAL | Participants received ALXN1840 once in each Period as a single oral dose under fasted conditions as follows: Period 1: ALXN1840 as a single EC tablet (Treatment A, reference). Period 2: ALXN1840 as three EC tablets (Treatment B, test). Participants were discharged following the 240-hour post-dose procedures (approximately 10 days after dosing in each period) unless it was medically necessary to extend the confinement. There was a washout period of at least 14 days between each ALXN1840 dosing. |
| Sequence 2 (BA) | EXPERIMENTAL | Participants received ALXN1840 once in each Period as a single oral dose under fasted conditions as follows: Period 1: ALXN1840 as three EC tablets (Treatment B, test). Period 2: ALXN1840 as a single EC tablet (Treatment A, reference). Participants were discharged following the 240-hour post-dose procedures (approximately 10 days after dosing in each period) unless it was medically necessary to extend the confinement. There was a washout period of at least 14 days between each ALXN1840 dosing. |
| Cohort 1: Japanese Participants | EXPERIMENTAL | All Japanese participants will receive a single dose of ALXN1840 15 milligrams (mg) in Dosing Period 1 and will receive a single dose of ALXN1840 60 mg in Dosing Period 2. |
| Cohort 2: Non-Japanese Participants | EXPERIMENTAL | All non-Japanese participants will receive a single dose of ALXN1840 15 mg in Dosing Period 1 and will receive a single dose of ALXN1840 60 mg in Dosing Period 2. |
| Sequence 1: ABC | EXPERIMENTAL | Participants received each treatment on 1 occasion: Period 1 (Treatment A): ALXN1840 following an overnight fast. Period 2 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. Period 3 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. There was a washout period of at least 14 days between each ALXN1840 dosing. |
| Sequence 2: ACB | EXPERIMENTAL | Participants received each treatment on 1 occasion: Period 1 (Treatment A): ALXN1840 following an overnight fast. Period 2 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 3 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. There was a washout period of at least 14 days between each ALXN1840 dosing. |
| Sequence 3: BAC | EXPERIMENTAL | Participants received each treatment on 1 occasion: Period 1 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. Period 2 (Treatment A): ALXN1840 following an overnight fast. Period 3 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. There was a washout period of at least 14 days between each ALXN1840 dosing. |
| Sequence 4: BCA | EXPERIMENTAL | Participants received each treatment on 1 occasion: Period 1 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. Period 2 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 3 (Treatment A): ALXN1840 following an overnight fast. There was a washout period of at least 14 days between each ALXN1840 dosing. |
| Sequence 5: CAB | EXPERIMENTAL | Participants received each treatment on 1 occasion: Period 1 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 2 (Treatment A): ALXN1840 following an overnight fast. Period 3 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. There was a washout period of at least 14 days between each ALXN1840 dosing. |
| Sequence 6: CBA | EXPERIMENTAL | Participants received each treatment on 1 occasion: Period 1 (Treatment C): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 2 (Treatment B): Omeprazole once daily in the morning of Days -5 to -1 following an overnight fast, omeprazole at Hour -1 on Day 1 following an overnight fast, and ALXN1840 at Hour 0 on Day 1, following an overnight fast. Period 3 (Treatment A): ALXN1840 following an overnight fast. There was a washout period of at least 14 days between each ALXN1840 dosing. |
| Name | Type | Description |
|---|---|---|
| ALXN1840 | DRUG | Administered orally as tablets. |
| Bupropion Hydrochloride | DRUG | Bupropion hydrochloride will be administered orally as a single dose as one 150 milligrams (mg) tablet with 240 milliliters of water (fasting). |
| Placebo | DRUG | Placebo will be administered orally. |
| Moxifloxacin | DRUG | Moxifloxacin (400 milligrams) will be administered orally. |
| Celecoxib | DRUG | Celecoxib was administered orally as a single dose as one 200-mg tablet with 240 mL of water (fasting). |
| Omeprazole | DRUG | Omeprazole (20 milligrams) was administered orally as a delayed-release capsule in the morning of Days -5 to -1 and at Hour -1 on Day 1. |
Inclusion Criteria: 1. Diagnosis of WD by Leipzig Criteria ≥ 4. 2. Able to reside in the clinical research unit for intensive metabolic monitoring of copper and molybdenum. 3. Participants willing to adhere to copper/molybdenum-controlled diet during the study. 4. Willing and able to follow protoco...
ALXN1840 is an investigational small molecule being developed for Wilson disease. It is currently in Phase 1 clinical development, with studies conducted in healthy adults to evaluate its safety, tolerability, and pharmacological properties. The drug is not yet approved and remains under clinical investigation.
ALXN1840 is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker AZN. The company is conducting Phase 1 clinical trials to evaluate the drug's properties in healthy volunteers.
ALXN1840 is in Phase 1 clinical development. All five clinical trials associated with the drug have been completed, with a total enrollment of 188 participants. The studies were randomized, double-blind, and controlled, focusing on healthy adults.
ALXN1840 has been studied in five completed Phase 1 trials. These include NCT04560816, a cardiac effects study in healthy US adults; NCT04610580, a bioavailability study in Australia; NCT05303324, a dose strength study in the UK; and NCT05319899, a study with and without omeprazole in the US.
ALXN1840 is the primary name used for this investigational drug. No alternative names have been reported for this compound in the available clinical trial information.