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The study will assess the relative bioavailability of 2 different formulations of ALXN1840 in healthy participants.
This is a two-way crossover study consisting of 2 dosing periods assessing a test and reference formulation of ALXN1840. A dose-proportionality parallel group design extension period will be conducted following completion of the two-way crossover period of the study and will assess 5 different ascending doses of ALXN1840. There will be at least a 14-day washout following doses between Periods 1 and 2 and also at least a 14-day washout following the dose in Period 2 and the following dose in the Dose-Proportionality Extension Period.
Safety will be assessed throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALXN1840 | Drug | ALXN1840 will be administered orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Two-way Crossover Period: Maximum Observed Concentration (Cmax) For Plasma Total Molybdenum (Mo) | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via inductively coupled plasma-mass spectroscopy (ICP-MS). | predose (0.5 hour) and up to 336 hours postdose |
| Two-way Crossover Period: Cmax for PUF Mo | Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS. | predose (0.5 hour) and up to 336 hours postdose |
| Two-way Crossover Period: Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | predose (0.5 hour) and up to 336 hours postdose |
| Two-way Crossover Period: AUCt for Plasma PUF Mo | Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS. | predose (0.5 hour) and up to 336 hours postdose |
| Two-way Crossover Period: Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | predose (0.5 hour) and up to 336 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Proportionality Extension Period: Cmax For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | predose (0.5 hour) and up to 336 hours postdose |
| Dose-Proportionality Extension Period: Cmax For Plasma PUF Mo |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eugene S. Swenson, MD, PhD | Alexion Pharmaceuticals, Inc. | Study Director |
| Masood Sadaat, MD, MSc | Alexion Pharmaceuticals, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nucleus Network Pty Ltd. | Melbourne | Victoria | 3004 | Australia |
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The study included a 2-way crossover period and a dose-proportionality extension period. Participants were randomized to 1 of the 2 treatment sequences (A-B) or (B-A) in crossover period with washout between. Participants were scheduled to receive either treatment A or B on Day 1 of each dosing period. After a 14-day washout period, participants were rerandomized in dose-proportionality extension period to receive treatment C, D, E, or F.
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| ID | Title | Description |
|---|---|---|
| FG000 | Crossover: ALXN1840 Test Formulation (Treatment A) First, Then Reference Formulation (Treatment B) | Participants received a single dose of ALXN1840 test formulation (15 milligrams [mg]; 12 × 1.25 mg enteric-coated [EC] mini-tablets) orally on Day 1 of the first dosing period. Then, participants received a single dose of ALXN1840 reference formulation (15 mg EC tablet) orally on Day 1 of the second dosing period. There was a 14-day washout between the two dosing periods. |
| FG001 | Crossover: ALXN1840 Reference Formulation (Treatment B) First, Then Test Formulation (Treatment A) | Participants received a single dose of ALXN1840 reference formulation (15 mg EC tablet) orally on Day 1 of the first dosing period. Then, participants received a single dose of ALXN1840 test formulation (15 mg; 12 × 1.25 mg EC mini-tablets) orally on Day 1 of second dosing period. There was a 14-day washout between the two dosing periods. |
| FG002 | Dose-proportionality Extension: ALXN1840 2.5 mg (Treatment C) | Participants received a single dose of ALXN1840 2.5 mg (2 × 1.25 mg EC mini-tablets) orally on Day 1. |
| FG003 | Dose-proportionality Extension: ALXN1840 5 mg (Treatment D) | Participants received a single dose of ALXN1840 5 mg (4 × 1.25 mg EC mini-tablets) orally on Day 1. |
| FG004 | Dose-proportionality Extension: ALXN1840 10 mg (Treatment E) | Participants received a single dose of ALXN1840 10 mg (8 × 1.25 mg EC mini-tablets) orally on Day 1. |
| FG005 | Dose-proportionality Extension: ALXN1840 30 mg (Treatment F) | Participants received a single dose of ALXN1840 30 mg (24 × 1.25 mg EC mini-tablets) orally on Day 1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Two-way Crossover Period |
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| Washout Before Extension Period |
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| Dose-Proportionality Extension Period |
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The Safety Set included all participants who received at least 1 dose of ALXN1840.
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Population | Crossover: Participants first received a single dose of ALXN1840 test formulation (15 mg; 12 × 1.25 mg EC mini-tablets) orally on Day 1 of Period 1 and then after a washout period of 14 days, received a single dose of ALXN1840 reference formulation (15 mg EC tablet) orally on Day 1 of Period 2. Dose-proportionality extension: Participants received a single dose of ALXN1840 2.5, 5, 10, or 30 mg orally on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Two-way Crossover Period: Maximum Observed Concentration (Cmax) For Plasma Total Molybdenum (Mo) | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via inductively coupled plasma-mass spectroscopy (ICP-MS). | The Pharmacokinetic/Pharmacodynamic Set for the Two-way Crossover Periods (PKDS-CO) included all participants who received at least 1 dose of ALXN1840 in the Two-way Crossover Periods and had evaluable pharmacokinetic (PK) data for total and/or plasma ultrafiltrate (PUF) Mo (as surrogate measures of ALXN1840 PK) in plasma. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms (ng)/milliliter (mL) | predose (0.5 hour) and up to 336 hours postdose |
|
Baseline up to Day 15
The Safety Set included all participants who received at least 1 dose of ALXN1840 and are presented by the treatment received at the time of the adverse event reporting.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Crossover: ALXN1840 Test Formulation (Treatment A) | Participants received a single dose of ALXN1840 test formulation (15 mg; 12 × 1.25 mg EC mini-tablets) orally on Day 1 of each dosing period in a crossover design. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals Inc. | Alexion Pharmaceuticals Inc. | +1 855-752-2356 | clinicaltrials@alexion.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 18, 2020 | Jun 8, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 11, 2021 | Jun 8, 2022 | SAP_001.pdf |
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This is a 2-period, 2-sequence, crossover study with a parallel group extension.
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| Parallel Dose-proportionality Extension: ALXN1840 Dose 4 | Experimental | Participants will receive a single dose of ALXN1840. |
|
|
Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS. |
| predose (0.5 hour) and up to 336 hours postdose |
| Dose-Proportionality Extension Period: AUCt For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | predose (0.5 hour) and up to 336 hours postdose |
| Dose-Proportionality Extension Period: AUCt For Plasma PUF Mo | Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS. | predose (0.5 hour) and up to 336 hours postdose |
| Dose-Proportionality Extension Period: AUCinf For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | predose (0.5 hour) and up to 336 hours postdose |
| Physician Decision |
|
| Withdrawal by Subject |
|
| Other than specified |
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| COMPLETED |
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| NOT COMPLETED |
|
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| Received at Least 1 Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 | Crossover: ALXN1840 Reference Formulation (Treatment B) | Participants received a single dose of ALXN1840 reference formulation (15 mg EC tablet) orally on Day 1 of each dosing period in a crossover deign. |
|
|
|
| Primary | Two-way Crossover Period: Cmax for PUF Mo | Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS. | The PKDS-CO included all participants who received at least 1 dose of ALXN1840 in the Two-way Crossover Periods and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
|
| Primary | Two-way Crossover Period: Area Under The Plasma Concentration Versus Time Curve From Time 0 To The Last Quantifiable Concentration (AUCt) For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | The PKDS-CO included all participants who received at least 1 dose of ALXN1840 in the Two-way Crossover Periods and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
|
| Primary | Two-way Crossover Period: AUCt for Plasma PUF Mo | Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS. | The PKDS-CO included all participants who received at least 1 dose of ALXN1840 in the Two-way Crossover Periods and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
|
| Primary | Two-way Crossover Period: Area Under The Plasma Concentration Versus Time Curve From Time 0 To Infinity (AUCinf) For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | The PKDS-CO included all participants who received at least 1 dose of ALXN1840 in the Two-way Crossover Periods and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
|
| Secondary | Dose-Proportionality Extension Period: Cmax For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | The Pharmacokinetic/Pharmacodynamic Set for the Dose-Proportionality Extension Period (PKDS-E) included all participants who receive at least 1 dose of ALXN1840 in the Dose-Proportionality Extension Period and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. | Posted | Mean | Standard Deviation | ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
| Secondary | Dose-Proportionality Extension Period: Cmax For Plasma PUF Mo | Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS. | The PKDS-E included all participants who receive at least 1 dose of ALXN1840 in the Dose-Proportionality Extension Period and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. | Posted | Mean | Standard Deviation | ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
| Secondary | Dose-Proportionality Extension Period: AUCt For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | The PKDS-E included all participants who receive at least 1 dose of ALXN1840 in the Dose-Proportionality Extension Period and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. | Posted | Mean | Standard Deviation | hours*ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
| Secondary | Dose-Proportionality Extension Period: AUCt For Plasma PUF Mo | Whole blood samples were collected for the measurement of plasma concentrations of PUF Mo via ICP-MS. | The PKDS-E included all participants who receive at least 1 dose of ALXN1840 in the Dose-Proportionality Extension Period and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. | Posted | Mean | Standard Deviation | hours*ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
| Secondary | Dose-Proportionality Extension Period: AUCinf For Plasma Total Mo | Whole blood samples were collected for the measurement of plasma concentrations of total Mo via ICP-MS. | The PKDS-E included all participants who receive at least 1 dose of ALXN1840 in the Dose-Proportionality Extension Period and had evaluable PK data for total and/or PUF molybdenum (as surrogate measures of ALXN1840 PK) in plasma. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. Only data for Treatments D, E, and F were collected for this Outcome Measure. | Posted | Mean | Standard Deviation | hours*ng/mL | predose (0.5 hour) and up to 336 hours postdose |
|
|
|
| 0 |
| 46 |
| 0 |
| 46 |
| 18 |
| 46 |
| EG001 | Crossover: ALXN1840 Reference Formulation (Treatment B) | Participants received a single dose of ALXN1840 reference formulation (15 mg EC tablet) orally on Day 1 of each dosing period in a crossover deign. | 0 | 46 | 0 | 46 | 20 | 46 |
| EG002 | Dose-proportionality Extension: ALXN1840 2.5 mg (Treatment C) | Participants received a single dose of ALXN1840 2.5 mg (2 × 1.25 mg EC mini-tablets) orally on Day 1. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG003 | Dose-proportionality Extension: ALXN1840 5 mg (Treatment D | Participants received a single dose of ALXN1840 5 mg (4 × 1.25 mg EC mini-tablets) orally on Day 1. | 0 | 11 | 0 | 11 | 5 | 11 |
| EG004 | Dose-proportionality Extension: ALXN1840 10 mg (Treatment E) | Participants received a single dose of ALXN1840 10 mg (8 × 1.25 mg EC mini-tablets) orally on Day 1. | 0 | 9 | 0 | 9 | 3 | 9 |
| EG005 | Dose-proportionality Extension: ALXN1840 30 mg (Treatment F) | Participants received a single dose of ALXN1840 30 mg (24 × 1.25 mg EC mini-tablets) orally on Day 1. | 0 | 11 | 0 | 11 | 4 | 11 |
| Hypoaesthesia | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Catheter site bruise | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Catheter site paraesthesia | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Feeling abnormal | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Feeling abnormal | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 24.0 | Systematic Assessment |
|
| Vessel puncture site pain | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Vessel puncture site reaction | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 24.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 24.0 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 24.0 | Systematic Assessment |
|
| Premenstrual pain | Reproductive system and breast disorders | MedDRA 24.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Procedural complication | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Folliculitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 24.0 | Systematic Assessment |
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| Cerumen impaction | Ear and labyrinth disorders | MedDRA 24.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Injection site thrombosis | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Physical deconditioning | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Tonsillolith | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Monocytosis | Blood and lymphatic system disorders | MedDRA 24.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 24.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 24.0 | Systematic Assessment |
|
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