Healthy
Conditions
Keywords
ALXN1840, Enteric-coated tablet, Pharmacokinetics, Pharmacodynamics, Healthy
Brief summary
To assess the relative bioavailability of ALXN1840 administered orally as a single enteric-coated (EC) tablet (reference, Treatment A) versus three EC tablets (test, Treatment B).
Interventions
DRUGALXN1840
Participants received ALXN1840 at Hour 0 on Day 1 of the dosing period.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Body weight ≤ 100 kilograms (kg) and body mass index within the range 18-25 kg/meter squared, inclusive, at Screening. * Negative serum pregnancy test at Screening and Day -1 for all women of childbearing potential. * Willing to adhere to contraception requirements. * Satisfactory medical assessment with no clinically significant or relevant abnormalities.
Exclusion criteria
* Current or recurrent/chronic disease * Positive test for hepatitis B surface antigen or human immunodeficiency virus antibody at Screening. * Acute or chronic hepatitis C virus infection. * History of hypersensitivity to ALXN1840 or its excipients or any significant allergic reaction. * Use of prescription medications (excluding oral contraceptives) within 14 days prior to dosing on Day 1, except with prior approval of the Sponsor. * Participation (that is, last protocol-required study visit) in a clinical study within 90 days before initiation of dosing on Day 1. * Serum ceruloplasmin value outside of the normal range at Screening * Female participants who were breastfeeding. * Prior exposure to ALXN1840. * Major surgery or hospitalization within 90 days prior to dosing on Day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed (Plasma) Concentration (Cmax) of Total Molybdenum | Up to 240 hours postdose | 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). |
| Area Under The Plasma Concentration Versus Time Curve From Time 0 (Dosing) to the Last Quantifiable Concentration (AUCt) of Total Molybdenum | Up to 240 hours postdose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Baseline up to Day 43 | An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was an AE that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. A related TEAE was defined as having a reasonable possibility the study intervention caused the AE as assessed by the investigator. Serious AEs (SAEs) were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Countries
United Kingdom
Participant flow
Pre-assignment details
Participants were randomized to 1 of 2 treatment sequences (A-B) or (B-A) in a crossover study design during 2 dosing periods. Participants were scheduled to receive either treatment A or B on Day 1 of each dosing period. There was a washout of at least 14 days between the dosing periods.
Participants by arm
| Arm | Count |
|---|---|
| ALXN1840 Treatment Sequence A-B Period 1: Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1 (Treatment A).
Period 2: Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1 (Treatment B). There was a washout of at least 14 days between the dosing periods. | 25 |
| ALXN1840 Treatment Sequence B-A Period 1: Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1 (Treatment B).
Period 2: Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1 (Treatment A). There was a washout of at least 14 days between the dosing periods. | 23 |
| Total | 48 |
Baseline characteristics
| Characteristic | ALXN1840 Treatment Sequence A-B | ALXN1840 Treatment Sequence B-A | Total |
|---|---|---|---|
| Age, Continuous | 28.7 years STANDARD_DEVIATION 6.63 | 28.1 years STANDARD_DEVIATION 6.04 | 28.4 years STANDARD_DEVIATION 6.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 23 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 23 | 0 / 23 | 0 / 25 |
| other Total, other adverse events | 7 / 25 | 5 / 23 | 4 / 23 | 8 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 23 | 0 / 23 | 0 / 25 |
Outcome results
Primary
Area Under The Plasma Concentration Versus Time Curve From Time 0 (Dosing) to the Last Quantifiable Concentration (AUCt) of Total Molybdenum
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.
Time frame: Up to 240 hours postdose
Population: The Pharmacokinetic Population included all participants who had sufficient plasma samples to enable the calculation of PK parameters of at least the AUC for at least 1 Treatment Period. Participants were grouped by period for each treatment for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 Treatment A | Area Under The Plasma Concentration Versus Time Curve From Time 0 (Dosing) to the Last Quantifiable Concentration (AUCt) of Total Molybdenum | 7054.5 hours*ng/mL | Standard Deviation 3634.92 |
| ALXN1840 Treatment B | Area Under The Plasma Concentration Versus Time Curve From Time 0 (Dosing) to the Last Quantifiable Concentration (AUCt) of Total Molybdenum | 6990.5 hours*ng/mL | Standard Deviation 3020.7 |
Primary
Maximum Observed (Plasma) Concentration (Cmax) of Total Molybdenum
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).
Time frame: Up to 240 hours postdose
Population: The Pharmacokinetic Population included all participants who had sufficient plasma samples to enable the calculation of PK parameters of at least the area under the plasma concentration versus time curve (AUC) for at least 1 Treatment Period. Participants were grouped by period for each treatment for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1840 Treatment A | Maximum Observed (Plasma) Concentration (Cmax) of Total Molybdenum | 173.10 nanograms (ng)/milliliter (mL) | Standard Deviation 78.098 |
| ALXN1840 Treatment B | Maximum Observed (Plasma) Concentration (Cmax) of Total Molybdenum | 174.27 nanograms (ng)/milliliter (mL) | Standard Deviation 62.956 |
Secondary
Number of Participants With a Treatment-Emergent Adverse Event (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was an AE that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. A related TEAE was defined as having a reasonable possibility the study intervention caused the AE as assessed by the investigator. Serious AEs (SAEs) were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Baseline up to Day 43
Population: The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ALXN1840 Treatment A | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any serious TEAE (SAE) | 0 Participants |
| ALXN1840 Treatment A | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any related TEAE | 4 Participants |
| ALXN1840 Treatment A | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any TEAE | 7 Participants |
| ALXN1840 Treatment A | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any TEAE leading to death | 0 Participants |
| ALXN1840 Treatment B | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any TEAE | 5 Participants |
| ALXN1840 Treatment B | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any TEAE leading to death | 0 Participants |
| ALXN1840 Treatment B | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any serious TEAE (SAE) | 0 Participants |
| ALXN1840 Treatment B | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any related TEAE | 0 Participants |
| Period 2: ALXN1840 Treatment A | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any serious TEAE (SAE) | 0 Participants |
| Period 2: ALXN1840 Treatment A | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any TEAE leading to death | 0 Participants |
| Period 2: ALXN1840 Treatment A | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any related TEAE | 1 Participants |
| Period 2: ALXN1840 Treatment A | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any TEAE | 4 Participants |
| Period 2: ALXN1840 Treatment B | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any TEAE leading to death | 0 Participants |
| Period 2: ALXN1840 Treatment B | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any serious TEAE (SAE) | 0 Participants |
| Period 2: ALXN1840 Treatment B | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any TEAE | 8 Participants |
| Period 2: ALXN1840 Treatment B | Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) | Any related TEAE | 1 Participants |