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This is a Phase 1, randomized, 2-period, 2-sequence, cross-over study designed to determine the effect of ALXN1840 on the metabolism of bupropion, a sensitive cytochrome P450 2B6 (CYP2B6) substrate, in healthy male and female participants. The safety and tolerability of ALXN1840 will be determined along with ALXN1840 pharmacokinetics (PK) in plasma as measured via total molybdenum with the coadministration of bupropion.
The study is being 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 bupropion (victim) kinetics in healthy male and female participants.
The study has 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 bupropion, and an End of Study Visit (Day 15 ± 2 days) after Period 2 dosing. Participants will report to the clinical research unit on the day prior (Day -1) to both dosing periods. All participants will receive 1 treatment in each study period; treatment order will be defined based on randomization: Treatments A and B.
The time between dosing bupropion alone or in combination with ALXN1840 in each treatment sequence will be a minimum of 14 days.
The PK profile of ALXN1840 and bupropion will be determined by blood sampling following single dose administration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Experimental | Participants will receive bupropion. |
|
| Treatment B | Experimental | Participants will receive bupropion with ALXN1840. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALXN1840 | Drug | ALXN1840 will be administered orally as a single dose as 4 x 15 mg enteric-coated tablets with 240 milliliters of water (fasting), for a total dose of 60 mg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840 | Pre-dose (Day 1) up to 336 hours post-dose | |
| Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) of Bupropion With and Without the Coadministration of ALXN1840 | Pre-dose (Day 1) up to 336 hours post-dose | |
| Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUCinf) of Bupropion With and Without the Coadministration of ALXN1840 | Pre-dose (Day 1) up to 336 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840 | Pre-dose (Day 1) up to 336 hours post-dose | |
| AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840 | Pre-dose (Day 1) up to 336 hours post-dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Austin | Texas | 78744 | United States |
Eligible participants were randomized to 1 of the two treatment sequences (A-B or B-A) on Day 1 prior to dosing in Period 1. Participants were scheduled to receive a single treatment (A or B) on Day 1 of each treatment period in the crossover design.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Sequence A-B | Treatment A: Participants received a single oral dose of 1 × 150 milligrams (mg) bupropion hydrochloride (HCl) salt tablet in a fasted state on Day 1 of treatment period 1. Treatment B: Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet coadministered with 4 × 15 mg enteric coated (EC) tablets of ALXN1840 in a fasted state on Day 1 of treatment period 2. There was a washout period of 14 days between the 2 treatment periods. |
| FG001 | Treatment Sequence B-A | Treatment B: Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet coadministered with 4 × 15 mg EC tablets of ALXN1840 in a fasted state on Day 1 of treatment period 1. Treatment A: Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet in a fasted state on Day 1 of treatment period 2. There was a washout period of 14 days between the 2 treatment periods. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety set included all participants who received at least 1 dose of study intervention.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Sequence A-B | Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet in a fasted state on Day 1 of treatment period 1. Treatment B: Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet coadministered with 4 × 15 mg EC tablets of ALXN1840 in a fasted state on Day 1 of treatment period 2. There was a washout period of 14 days between the 2 treatment periods. |
| 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 | Maximum Observed Plasma Concentration (Cmax) of Bupropion With and Without the Coadministration of ALXN1840 | Pharmacokinetic (PK) analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms (ng)/milliliter (mL) | Pre-dose (Day 1) up to 336 hours post-dose |
|
Day 1 up to Day 15
Safety set included all participants who received at least 1 dose of study intervention.
All randomized participants except 8 received both assigned doses; 4 participants received only Treatment A and 4 participants received only Treatment B. In total, 50 participants received Treatment A and 50 participants received Treatment B. An AE that occurred during the washout period between drugs was considered treatment emergent to the last drug given.
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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 | Treatment A: Bupropion HCl | Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet in a fasted state on Day 1 of treatment period 1 or 2. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chalazion | Eye 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 | Mar 16, 2021 | Oct 17, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 21, 2020 | Oct 17, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006527 | Hepatolenticular Degeneration |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| C020809 | tetrathiomolybdate |
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
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|
| 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). |
|
|
| AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840 | Pre-dose (Day 1) up to 336 hours post-dose |
| Cmax of Plasma Total Molybdenum With Coadministration of Bupropion | Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only. | Pre-dose (Day 1) up to 336 hours post-dose |
| AUCt of Plasma Total Molybdenum With Coadministration of Bupropion | Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only. | Pre-dose (Day 1) up to 336 hours post-dose |
| AUCinf of Plasma Total Molybdenum With Coadministration of Bupropion | Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only. | Pre-dose (Day 1) up to 336 hours post-dose |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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 any AE that began or worsened on or after the first dose of treatment until the end of study (EOS) or early termination (ET). 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. | Day 1 up to Day 15 |
| BG001 | Treatment Sequence B-A | Treatment B: Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet coadministered with 4 × 15 mg EC tablets of ALXN1840 in a fasted state on Day 1 of treatment period 1. Treatment A: Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet in a fasted state on Day 1 of treatment period 2. There was a washout period of 14 days between the 2 treatment periods. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet coadministered with 4 × 15 mg EC tablets of ALXN1840 in a fasted state on Day 1 of treatment period 1 or 2. |
|
|
|
| Primary | Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) of Bupropion With and Without the Coadministration of ALXN1840 | PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | Pre-dose (Day 1) up to 336 hours post-dose |
|
|
|
|
| Primary | Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUCinf) of Bupropion With and Without the Coadministration of ALXN1840 | PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | Pre-dose (Day 1) up to 336 hours post-dose |
|
|
|
|
| Secondary | Cmax of Hydroxybupropion With and Without the Coadministration of ALXN1840 | PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (Day 1) up to 336 hours post-dose |
|
|
|
| Secondary | AUCt of Hydroxybupropion With and Without the Coadministration of ALXN1840 | PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | Pre-dose (Day 1) up to 336 hours post-dose |
|
|
|
| Secondary | AUCinf of Hydroxybupropion With and Without the Coadministration of ALXN1840 | PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | Pre-dose (Day 1) up to 336 hours post-dose |
|
|
|
| Secondary | Cmax of Plasma Total Molybdenum With Coadministration of Bupropion | Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only. | PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (Day 1) up to 336 hours post-dose |
|
|
|
| Secondary | AUCt of Plasma Total Molybdenum With Coadministration of Bupropion | Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only. | PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | Pre-dose (Day 1) up to 336 hours post-dose |
|
|
|
| Secondary | AUCinf of Plasma Total Molybdenum With Coadministration of Bupropion | Plasma total molybdenum was assessed as surrogate measures for ALXN1840 PK following coadministration with bupropion HCl salt tablet (Treatment B) only. | PK analysis set included all participants who had sufficient plasma samples to have evaluable PK data for bupropion and/or total molybdenum (as a measure of ALXN1840) in plasma. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | Pre-dose (Day 1) up to 336 hours post-dose |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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 any AE that began or worsened on or after the first dose of treatment until the end of study (EOS) or early termination (ET). 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. | Safety set included all participants who received at least 1 dose of study intervention. | Posted | Number | participants | Day 1 up to Day 15 |
|
|
|
| 0 |
| 50 |
| 0 |
| 50 |
| 8 |
| 50 |
| EG001 | Treatment B: Bupropion HCl + ALXN1840 | Participants received a single oral dose of 1 × 150 mg bupropion HCl salt tablet coadministered with 4 × 15 mg EC tablets of ALXN1840 in a fasted state on Day 1 of treatment period 1 or 2. | 0 | 50 | 0 | 50 | 11 | 50 |
| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Anal haemorrhage | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 24.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
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| D002493 |
| Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008664 | Metal Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |