Healthy
Conditions
Keywords
ALXN1840, WTX101, Omeprazole
Brief summary
This was single-center, open-label, randomized, 3-period, 3-treatment, 6-sequence crossover study evaluating the PK of single doses of WTX101 in healthy participants based on the measurement of plasma total Molybdenum.
Interventions
DRUGALXN1840
ALXN1840 (60 milligrams) was administered orally as non-coated capsules at Hour 0 on Day 1.
DRUGOmeprazole
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.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This was single-center, open-label, randomized, 3-period, 3-treatment, 6-sequence crossover study.
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Non-smoker * Medically healthy with no clinically significant laboratory profiles, vital signs, or electrocardiograms. * Body mass index ≥ 18 and ≤ 32.0 kilograms/meter squared. * Willing and able to adhere to contraception requirements.
Exclusion criteria
* Participant was mentally or legally incapacitated * History or presence of clinically significant medical or psychiatric condition or disease. * History of any illness that might have interfered with drug absorption. * History or presence of hypersensitivity or idiosyncratic reaction to the study medications, study medication excipients. * History or presence of alcoholism or drug abuse. * Female participants who were pregnant or lactating. * Positive results at screening for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus. * Serum ceruloplasmin and copper values outside of the normal range at screening. * On a diet incompatible with the on-study diet within the 28 days prior to the first ALXN1840 dose and throughout the study; unable to consume the contents of a high-fat breakfast. * Participation in a previous clinical trial with ALXN1840.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Total Molybdenum (Mo) | Predose (0 hour) up to 192 hours postdose | AUC0-t was calculated by the linear trapezoidal method. |
| Maximum Measured Plasma Concentration (Cmax) of Total Mo | Predose (0 hour) up to 192 hours postdose | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Day 1 through 14 days following final dose (up to Day 43) | 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. |
Countries
United States
Participant flow
Pre-assignment details
Participants were randomized to one of 6 treatment sequences.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence 1: ABC Participants received each treatment on 1 occasion:
Period 1 (Treatment A): ALXN1840 60 mg (2 x 30 mg capsules) on Day 1 following an overnight fast. Period 2 (Treatment B): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, following an overnight fast. Period 3 (Treatment C): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) 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. | 3 |
| Treatment Sequence 2: ACB Participants received each treatment on 1 occasion:
Period 1 (Treatment A): ALXN1840 60 mg (2 x 30 mg capsules) on Day 1 following an overnight fast. Period 2 (Treatment C): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 3 (Treatment B): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, following an overnight fast.
There was a washout period of at least 14 days between each ALXN1840 dosing. | 3 |
| Treatment Sequence 3: BAC Participants received each treatment on 1 occasion:
Period 1 (Treatment B): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, following an overnight fast. Period 2 (Treatment A): ALXN1840 60 mg (2 x 30 mg capsules) on Day 1 following an overnight fast. Period 3 (Treatment C): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) 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. | 3 |
| Treatment Sequence 4: BCA Participants received each treatment on 1 occasion:
Period 1 (Treatment B): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, following an overnight fast. Period 2 (Treatment C): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 3 (Treatment A): ALXN1840 60 mg (2 x 30 mg capsules) on Day 1 following an overnight fast.
There was a washout period of at least 14 days between each ALXN1840 dosing. | 3 |
| Treatment Sequence 5: CAB Participants received each treatment on 1 occasion:
Period 1 (Treatment C): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 2 (Treatment A): ALXN1840 60 mg (2 x 30 mg capsules) on Day 1 following an overnight fast. Period 3 (Treatment B): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, following an overnight fast.
There was a washout period of at least 14 days between each ALXN1840 dosing. | 3 |
| Treatment Sequence 6: CBA Participants received each treatment on 1 occasion:
Period 1 (Treatment C): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, approximately 30 minutes after the start of a high-fat breakfast. Period 2 (Treatment B): Omeprazole 20 mg (1 x 20 mg delayed-release capsule) QD in the morning of Days -5 to -1 following an overnight fast, omeprazole 20 mg at Hour -1 on Day 1 following an overnight fast, and ALXN1840 60 mg (2 x 30 mg capsules) at Hour 0 on Day 1, following an overnight fast. Period 3 (Treatment A): ALXN1840 60 mg (2 x 30 mg capsules) on Day 1 following an overnight fast.
There was a washout period of at least 14 days between each ALXN1840 dosing. | 3 |
| Total | 18 |
Baseline characteristics
| Characteristic | Treatment Sequence 1: ABC | Treatment Sequence 2: ACB | Treatment Sequence 3: BAC | Treatment Sequence 4: BCA | Treatment Sequence 5: CAB | Treatment Sequence 6: CBA | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.7 years STANDARD_DEVIATION 4.16 | 31.3 years STANDARD_DEVIATION 10.21 | 25.7 years STANDARD_DEVIATION 2.52 | 36.0 years STANDARD_DEVIATION 14.11 | 35.0 years STANDARD_DEVIATION 17.69 | 40.0 years STANDARD_DEVIATION 12.53 | 33.1 years STANDARD_DEVIATION 10.75 |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 18 | 5 / 18 | 6 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Total Molybdenum (Mo)
AUC0-t was calculated by the linear trapezoidal method.
Time frame: Predose (0 hour) up to 192 hours postdose
Population: Pharmacokinetic (PK) analysis population included all participants who completed at least 2 periods of the study and had sufficient data for the determination of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: ALXN1840 (Fasted) | Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Total Molybdenum (Mo) | 14531 hours*ng/mL | Standard Deviation 6886 |
| Treatment B: Omeprazole + ALXN1840 (Fasted) | Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Total Molybdenum (Mo) | 18537 hours*ng/mL | Standard Deviation 4303 |
| Treatment C: Omeprazole + ALXN1840 (Fed) | Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Total Molybdenum (Mo) | 14536 hours*ng/mL | Standard Deviation 3663 |
Comparison: Analysis was performed using analysis of variance (ANOVA).90% CI: [118.94, 166.26]
Comparison: Analysis was performed using ANOVA.90% CI: [65.67, 91.8]
Primary
Maximum Measured Plasma Concentration (Cmax) of Total Mo
Time frame: Predose (0 hour) up to 192 hours postdose
Population: PK analysis population included all participants who completed at least 2 periods of the study and had sufficient data for the determination of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: ALXN1840 (Fasted) | Maximum Measured Plasma Concentration (Cmax) of Total Mo | 330 ng/mL | Standard Deviation 124 |
| Treatment B: Omeprazole + ALXN1840 (Fasted) | Maximum Measured Plasma Concentration (Cmax) of Total Mo | 401 ng/mL | Standard Deviation 78.3 |
| Treatment C: Omeprazole + ALXN1840 (Fed) | Maximum Measured Plasma Concentration (Cmax) of Total Mo | 385 ng/mL | Standard Deviation 71.3 |
Comparison: Analysis was performed using ANOVA.90% CI: [112.99, 145.52]
Comparison: Analysis was performed using ANOVA.90% CI: [84.54, 108.88]
Primary
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 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.
Time frame: Day 1 through 14 days following final dose (up to Day 43)
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A: ALXN1840 (Fasted) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
| Treatment B: Omeprazole + ALXN1840 (Fasted) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 5 Participants |
| Treatment C: Omeprazole + ALXN1840 (Fed) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |