Healthy
Conditions
Keywords
ALXN1910, Safety, Pharmacokinetics, Pharmacodynamics, Japanese Descent
Brief summary
This is a Phase 1, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single ascending doses (SADs) of ALXN1910 subcutaneous (SC) and SAD of ALXN1910 intravenous (IV).
Interventions
DRUGALXN1910
Participants will receive a single dose of ALXN1910 IV or ALXN1910 SC according to their assigned cohort.
DRUGPlacebo
Participants will receive Placebo IV or Placebo SC according to their assigned cohort.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants * Participants of Japanese descent are defined as: First generation (born to 2 Japanese parents and 4 Japanese grandparents). * Participants of Japanese descent must be between 20 and 55 years of age.
Exclusion criteria
* Current or recurrent disease * Current or relevant history of physical or psychiatric illness. * Any other significant disease or disorder that, in the opinion of the Investigator, may put the participant at risk. * History of significant allergic reaction (eg, anaphylaxis or angioedema) to any product (eg, food, pharmaceutical). * Female participants who are pregnant or breastfeeding. * Major surgery or hospitalization within 90 days prior to dosing on Day1. * History of exposure to asfotase alfa. * History of allergy or hypersensitivity to excipients of asfotase alfa or ALXN1910 (eg,sodium phosphate, sodium chloride).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 1 (postdose) through Day 75 | The safety and tolerability of ALXN1910 was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Observed Serum Concentration (Tmax) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The Tmax was assed as PK parameter of single ascending doses of ALXN1910. |
| Apparent Terminal Elimination Half Life (t1/2) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The t1/2 was assed as PK parameter of single ascending doses of ALXN1910. |
| Terminal-phase Elimination Rate Constant (λz) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The λz was assed as PK parameter of single ascending doses of ALXN1910. |
| AUC From Time Zero to the Last Quantifiable Concentratio (AUCt) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The AUCt was assed as PK parameter of single ascending doses of ALXN1910. |
| AUC From Time Zero Extrapolated to Infinity (AUC∞) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The AUC∞ was assed as PK parameter of single ascending doses of ALXN1910. |
| AUC From Time Zero to 168h (AUC0-168) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The AUC0-168 was assed as PK parameter of single ascending doses of ALXN1910. |
| Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The %AUCex was assed as PK parameter of single ascending doses of ALXN1910. |
| Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The CL or CL/F was assed as PK parameter of single ascending doses of ALXN1910. |
| Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The Vd or Vd/F was assed as PK parameter of single ascending doses of ALXN1910. |
| Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75 | The plasma concentrations of PPi was assesed. |
| Plasma Concentration of Pyridoxal (PL) | Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75 | The plasma concentrations of PL was assessed. |
| Maximum Observed Serum Concentration (Cmax) | Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75 | The Cmax was assessed as PK parameter of single ascending doses of ALXN1910. |
| Plasma Concentration of Pyridoxic Acid (PA) | Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75 | The plasma concentrations of PA was assessed. |
| Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) | Day 1 (postdose) through Day 75 | The ADAs of ALXN1910 was assessed as immunogenicity parameter. Treatment-emergent ADA Responses is defined as a positive result in the ADA assay post first dose, when baseline results are negative or missing. |
| Geometric Mean Ratio (GMR) of Area Under the Curve (AUC∞) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1910 | Up to Day 75 | The absolute bioavailability GMR AUC∞ of ALXN1910 SC was assessed. |
| Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants | Up to Day 75 | Quantitative assessment of PK parameter (Cmax) was assessed between Japanese and non-Japanese participants. |
| AUC From Time Zero to the Last Quantifiable Concentration (AUCt) in Japanese and Non-Japanese Participants | Up to Day 75 | Quantitative assessment of PK parameter (AUCt) was assessed between Japanese and non-Japanese participants. |
| AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants | Up to Day 75 | Quantitative assessment of PK parameter (AUC∞) was assessed between Japanese and non-Japanese participants. |
| Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 2, 15, 22, 43, and 75 | Change from baseline in PD parameter Inorganic Pyrophosphate was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment. |
| Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 2, 15, 22, 43, and 75 | Change from baseline in PD parameter Pyridoxal-5-phosphate was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment |
| Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 2, 15, 22, 43, and 75 | Change from baseline in PD parameter Pyridoxal was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment. |
| Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 2, 15, 22, 43, and 75 | Change from baseline in PD parameter Pyridoxic Acid was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment. |
| Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75 | The plasma concentrations of PLP was assessed. |
Countries
United Kingdom
Participant flow
Recruitment details
Subjects who met all the inclusion and none of the exclusion criteria were randomized in 1 site. The study was conducted from 12 Apr 2022 to 07 Feb 2023.
Pre-assignment details
The screening period was up to 28 days. Informed consent form (ICF) was signed prior to screening procedures. Subjects received study drug in a randomised order. All the study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1- 5 mg Participants received a single dose of 5 mg of ALXN1910 IV. | 6 |
| Cohort 2- 15 mg SC Participants received a single dose of 15 mg of ALXN1910 SC. | 6 |
| Cohort 3- 15 mg IV Participant received a single dose of 15 mg of ALXN1910 IV. | 6 |
| Japanese Cohort 4- 15 mg SC Japanese participants received a single dose of 15 mg of ALXN1910 SC. | 6 |
| Cohort 5- 45 mg Participants received a single dose of 45 mg of ALXN1910 SC. | 6 |
| Cohort 6- 135 mg Participants received a single dose of 135 mg of ALXN1910 SC. | 6 |
| Pooled Placebo Participants received a single dose of matching Placebo IV or SC. | 12 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 4 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1- 5 mg | Cohort 2- 15 mg SC | Cohort 3- 15 mg IV | Japanese Cohort 4- 15 mg SC | Cohort 5- 45 mg | Cohort 6- 135 mg | Pooled Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous Age | 37.7 Years STANDARD_DEVIATION 9.69 | 33.0 Years STANDARD_DEVIATION 13.75 | 35.3 Years STANDARD_DEVIATION 8.89 | 31.8 Years STANDARD_DEVIATION 7.65 | 30.2 Years STANDARD_DEVIATION 4.4 | 34.0 Years STANDARD_DEVIATION 7.85 | 33.6 Years STANDARD_DEVIATION 6.27 | 33.6 Years STANDARD_DEVIATION 8.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 10 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 6 Participants | 0 Participants | 0 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 13 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 3 Participants | 0 Participants | 4 Participants | 4 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 6 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 |
| other Total, other adverse events | 3 / 6 | 3 / 6 | 4 / 6 | 3 / 6 | 5 / 6 | 4 / 6 | 8 / 12 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 12 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
The safety and tolerability of ALXN1910 was assessed.
Time frame: Day 1 (postdose) through Day 75
Population: All participants who received any amount of study intervention were included in the Safety Analysis Set. Participants were analyzed according to the study intervention received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1- 5 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAE outcome of Death | 0 Participants |
| Cohort 1- 5 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 3 Participants |
| Cohort 1- 5 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 1- 5 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 0 Participants |
| Cohort 1- 5 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 2- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAE outcome of Death | 0 Participants |
| Cohort 2- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 0 Participants |
| Cohort 2- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 2- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 3 Participants |
| Cohort 2- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 3- 15 mg IV | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 3- 15 mg IV | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 0 Participants |
| Cohort 3- 15 mg IV | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 4 Participants |
| Cohort 3- 15 mg IV | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAE outcome of Death | 0 Participants |
| Cohort 3- 15 mg IV | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Japanese Cohort 4- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAE outcome of Death | 0 Participants |
| Japanese Cohort 4- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 3 Participants |
| Japanese Cohort 4- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 0 Participants |
| Japanese Cohort 4- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Japanese Cohort 4- 15 mg SC | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 5- 45 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 5 Participants |
| Cohort 5- 45 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 5- 45 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAE outcome of Death | 0 Participants |
| Cohort 5- 45 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 5- 45 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 0 Participants |
| Cohort 6- 135 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 4 Participants |
| Cohort 6- 135 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 6- 135 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Cohort 6- 135 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 1 Participants |
| Cohort 6- 135 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAE outcome of Death | 0 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | AE Leading to Withdrawal of Study Drug | 0 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any Serious TEAE | 0 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAE outcome of Death | 0 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Any TEAE | 8 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | SAE Leading to Withdrawal of Study Drug | 0 Participants |
Secondary
Apparent Terminal Elimination Half Life (t1/2)
The t1/2 was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number of Participants Analyzed refers to the number of participants available for the specific Outcome measure for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | Apparent Terminal Elimination Half Life (t1/2) | 166.1 hour (h) | Geometric Coefficient of Variation 25.1 |
| Cohort 2- 15 mg SC | Apparent Terminal Elimination Half Life (t1/2) | 215.1 hour (h) | Geometric Coefficient of Variation 12.2 |
| Cohort 3- 15 mg IV | Apparent Terminal Elimination Half Life (t1/2) | 194.9 hour (h) | Geometric Coefficient of Variation 19.2 |
| Japanese Cohort 4- 15 mg SC | Apparent Terminal Elimination Half Life (t1/2) | 207.5 hour (h) | Geometric Coefficient of Variation 13.9 |
| Cohort 5- 45 mg | Apparent Terminal Elimination Half Life (t1/2) | 271.3 hour (h) | Geometric Coefficient of Variation 6 |
| Cohort 6- 135 mg | Apparent Terminal Elimination Half Life (t1/2) | 263.5 hour (h) | Geometric Coefficient of Variation 18.8 |
Secondary
AUC From Time Zero Extrapolated to Infinity (AUC∞)
The AUC∞ was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number of Participants Analyzed refers to the number of participants available for the specific Outcome measure for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | AUC From Time Zero Extrapolated to Infinity (AUC∞) | 89.43 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 22.2 |
| Cohort 2- 15 mg SC | AUC From Time Zero Extrapolated to Infinity (AUC∞) | 168.0 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 20.3 |
| Cohort 3- 15 mg IV | AUC From Time Zero Extrapolated to Infinity (AUC∞) | 244.5 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 13.8 |
| Japanese Cohort 4- 15 mg SC | AUC From Time Zero Extrapolated to Infinity (AUC∞) | 157.8 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 23.4 |
| Cohort 5- 45 mg | AUC From Time Zero Extrapolated to Infinity (AUC∞) | 517.8 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 12.4 |
| Cohort 6- 135 mg | AUC From Time Zero Extrapolated to Infinity (AUC∞) | 1699 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 19.8 |
Secondary
AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants
Quantitative assessment of PK parameter (AUC∞) was assessed between Japanese and non-Japanese participants.
Time frame: Up to Day 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number Analyzed refers to the number of participants available for the specific Outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1- 5 mg | AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants | 168.05 h × μg/mL |
| Cohort 2- 15 mg SC | AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants | 157.78 h × μg/mL |
95% CI: [63.17, 139.56]Mixed Models Analysis
Secondary
AUC From Time Zero to 168h (AUC0-168)
The AUC0-168 was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | AUC From Time Zero to 168h (AUC0-168) | 53.06 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 14.4 |
| Cohort 2- 15 mg SC | AUC From Time Zero to 168h (AUC0-168) | 40.83 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 65.6 |
| Cohort 3- 15 mg IV | AUC From Time Zero to 168h (AUC0-168) | 142.1 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 11.6 |
| Japanese Cohort 4- 15 mg SC | AUC From Time Zero to 168h (AUC0-168) | 49.73 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 35.3 |
| Cohort 5- 45 mg | AUC From Time Zero to 168h (AUC0-168) | 161.9 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 37.2 |
| Cohort 6- 135 mg | AUC From Time Zero to 168h (AUC0-168) | 573.3 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 37.9 |
Secondary
AUC From Time Zero to the Last Quantifiable Concentratio (AUCt)
The AUCt was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number of Participants Analyzed refers to the number of participants available for the specific Outcome measure for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | AUC From Time Zero to the Last Quantifiable Concentratio (AUCt) | 69.52 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 23 |
| Cohort 2- 15 mg SC | AUC From Time Zero to the Last Quantifiable Concentratio (AUCt) | 102.4 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 44.1 |
| Cohort 3- 15 mg IV | AUC From Time Zero to the Last Quantifiable Concentratio (AUCt) | 219.0 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 14.2 |
| Japanese Cohort 4- 15 mg SC | AUC From Time Zero to the Last Quantifiable Concentratio (AUCt) | 120.9 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 30.3 |
| Cohort 5- 45 mg | AUC From Time Zero to the Last Quantifiable Concentratio (AUCt) | 484.3 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 13.1 |
| Cohort 6- 135 mg | AUC From Time Zero to the Last Quantifiable Concentratio (AUCt) | 1606 hour*microgram/milliliter (h*μg/mL) | Geometric Coefficient of Variation 20.4 |
Secondary
AUC From Time Zero to the Last Quantifiable Concentration (AUCt) in Japanese and Non-Japanese Participants
Quantitative assessment of PK parameter (AUCt) was assessed between Japanese and non-Japanese participants.
Time frame: Up to Day 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1- 5 mg | AUC From Time Zero to the Last Quantifiable Concentration (AUCt) in Japanese and Non-Japanese Participants | 102.37 h × μg/mL |
| Cohort 2- 15 mg SC | AUC From Time Zero to the Last Quantifiable Concentration (AUCt) in Japanese and Non-Japanese Participants | 120.94 h × μg/mL |
95% CI: [73.93, 188.8]Mixed Models Analysis
Secondary
Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants
Change from baseline in PD parameter Inorganic Pyrophosphate was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment.
Time frame: Day 2, 15, 22, 43, and 75
Population: All treated participants for whom the PD profile of ALXN1910 can be adequately characterized were included in the PD Set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- 5 mg | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 15 | -0.357 μmol | Standard Error 0.101 |
| Cohort 1- 5 mg | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 43 | -0.327 μmol | Standard Error 0.101 |
| Cohort 1- 5 mg | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 22 | -0.355 μmol | Standard Error 0.106 |
| Cohort 1- 5 mg | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 75 | -0.329 μmol | Standard Error 0.114 |
| Cohort 1- 5 mg | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 2 | -0.195 μmol | Standard Error 0.101 |
| Cohort 2- 15 mg SC | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 75 | -0.015 μmol | Standard Error 0.147 |
| Cohort 2- 15 mg SC | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 2 | -0.152 μmol | Standard Error 0.101 |
| Cohort 2- 15 mg SC | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 15 | -0.251 μmol | Standard Error 0.101 |
| Cohort 2- 15 mg SC | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 22 | -0.176 μmol | Standard Error 0.101 |
| Cohort 2- 15 mg SC | Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants | Day 43 | -0.119 μmol | Standard Error 0.101 |
Secondary
Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants
Change from baseline in PD parameter Pyridoxal-5-phosphate was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment
Time frame: Day 2, 15, 22, 43, and 75
Population: All treated participants for whom the PD profile of ALXN1910 can be adequately characterized were included in the PD Set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 15 | -1.220 μmol | Standard Error 3.628 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 43 | -0.883 μmol | Standard Error 3.628 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 22 | -0.412 μmol | Standard Error 3.9 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 75 | 1.137 μmol | Standard Error 4.269 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 2 | -0.430 μmol | Standard Error 3.628 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 75 | 2.839 μmol | Standard Error 5.677 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 2 | -4.957 μmol | Standard Error 3.659 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 15 | 2.193 μmol | Standard Error 3.659 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 22 | 13.693 μmol | Standard Error 3.659 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants | Day 43 | 5.633 μmol | Standard Error 3.659 |
Secondary
Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants
Change from baseline in PD parameter Pyridoxal was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment.
Time frame: Day 2, 15, 22, 43, and 75
Population: All treated participants for whom the PD profile of ALXN1910 can be adequately characterized were included in the PD Set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 15 | -0.171 ng/mL | Standard Error 0.74 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 43 | -0.171 ng/mL | Standard Error 0.74 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 22 | 0.190 ng/mL | Standard Error 0.795 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 75 | -0.063 ng/mL | Standard Error 0.868 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 2 | -0.093 ng/mL | Standard Error 0.74 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 75 | 1.789 ng/mL | Standard Error 1.174 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 2 | -0.061 ng/mL | Standard Error 0.74 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 15 | 0.789 ng/mL | Standard Error 0.74 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 22 | 2.981 ng/mL | Standard Error 0.74 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants | Day 43 | 2.308 ng/mL | Standard Error 0.74 |
Secondary
Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants
Change from baseline in PD parameter Pyridoxic Acid was evaluated over time for Japanese and non-Japanese participants (Cohort 2 versus Cohort 4) on active treatment.
Time frame: Day 2, 15, 22, 43, and 75
Population: All treated participants for whom the PD profile of ALXN1910 can be adequately characterized were included in the PD Set.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- 5 mg | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 15 | 0.182 ng/mL | Standard Error 1.263 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 43 | 0.009 ng/mL | Standard Error 1.263 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 22 | -0.238 ng/mL | Standard Error 1.383 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 75 | 0.189 ng/mL | Standard Error 1.545 |
| Cohort 1- 5 mg | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 2 | -0.316 ng/mL | Standard Error 1.263 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 75 | 4.812 ng/mL | Standard Error 2.184 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 2 | -0.725 ng/mL | Standard Error 1.263 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 15 | 1.267 ng/mL | Standard Error 1.263 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 22 | 6.278 ng/mL | Standard Error 1.263 |
| Cohort 2- 15 mg SC | Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants | Day 43 | 4.190 ng/mL | Standard Error 1.263 |
Secondary
Geometric Mean Ratio (GMR) of Area Under the Curve (AUC∞) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1910
The absolute bioavailability GMR AUC∞ of ALXN1910 SC was assessed.
Time frame: Up to Day 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number Analyzed refers to the number of participants available for the specific Outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1- 5 mg | Geometric Mean Ratio (GMR) of Area Under the Curve (AUC∞) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1910 | 168.05 h × μg/mL |
| Cohort 2- 15 mg SC | Geometric Mean Ratio (GMR) of Area Under the Curve (AUC∞) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1910 | 244.51 h × μg/mL |
95% CI: [52.74, 89.56]Mixed Models Analysis
Secondary
Maximum Observed Serum Concentration (Cmax)
The Cmax was assessed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | Maximum Observed Serum Concentration (Cmax) | 1.034 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 16.5 |
| Cohort 2- 15 mg SC | Maximum Observed Serum Concentration (Cmax) | 0.3172 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 60.3 |
| Cohort 3- 15 mg IV | Maximum Observed Serum Concentration (Cmax) | 3.113 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 11.5 |
| Japanese Cohort 4- 15 mg SC | Maximum Observed Serum Concentration (Cmax) | 0.3807 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 31.8 |
| Cohort 5- 45 mg | Maximum Observed Serum Concentration (Cmax) | 1.230 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 32 |
| Cohort 6- 135 mg | Maximum Observed Serum Concentration (Cmax) | 4.257 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 38.3 |
Secondary
Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants
Quantitative assessment of PK parameter (Cmax) was assessed between Japanese and non-Japanese participants.
Time frame: Up to Day 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cohort 1- 5 mg | Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants | 0.32 μg/mL |
| Cohort 2- 15 mg SC | Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants | 0.38 μg/mL |
95% CI: [67.2, 214.43]Mixed Models Analysis
Secondary
Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs)
The ADAs of ALXN1910 was assessed as immunogenicity parameter. Treatment-emergent ADA Responses is defined as a positive result in the ADA assay post first dose, when baseline results are negative or missing.
Time frame: Day 1 (postdose) through Day 75
Population: All randomized/enrolled participants who received at least 1 dose of the study intervention and who after the dose have at least 1 reportable ADA result. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1- 5 mg | Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) | 0 Participants |
| Cohort 2- 15 mg SC | Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) | 0 Participants |
| Cohort 3- 15 mg IV | Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) | 0 Participants |
| Japanese Cohort 4- 15 mg SC | Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) | 0 Participants |
| Cohort 5- 45 mg | Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) | 0 Participants |
| Cohort 6- 135 mg | Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) | 0 Participants |
| Pooled Placebo | Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) | 0 Participants |
Secondary
Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex)
The %AUCex was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number of Participants Analyzed refers to the number of participants available for the specific Outcome measure for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex) | 24.03 Percentage (%) of AUC∞ | Geometric Coefficient of Variation 21.1 |
| Cohort 2- 15 mg SC | Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex) | 22.89 Percentage (%) of AUC∞ | Geometric Coefficient of Variation 73.2 |
| Cohort 3- 15 mg IV | Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex) | 10.41 Percentage (%) of AUC∞ | Geometric Coefficient of Variation 5.8 |
| Japanese Cohort 4- 15 mg SC | Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex) | 16.89 Percentage (%) of AUC∞ | Geometric Coefficient of Variation 31.8 |
| Cohort 5- 45 mg | Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex) | 6.418 Percentage (%) of AUC∞ | Geometric Coefficient of Variation 12.5 |
| Cohort 6- 135 mg | Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex) | 5.133 Percentage (%) of AUC∞ | Geometric Coefficient of Variation 39 |
Secondary
Plasma Concentration of Inorganic Pyrophosphate (PPi)
The plasma concentrations of PPi was assesed.
Time frame: Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PD profile of ALXN1910 can be adequately characterized were included in the PD Set. Here, Number Analyzed refers to the number of participants available for the specific Outcome measure for specific timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 5 | 1.232 micromole/Liter (umol/L) | Standard Deviation 0.1052 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 2 | 1.162 micromole/Liter (umol/L) | Standard Deviation 0.2057 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 15 | 1.326 micromole/Liter (umol/L) | Standard Deviation 0.0503 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 29 | 1.295 micromole/Liter (umol/L) | Standard Deviation 0.161 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 8 | 1.368 micromole/Liter (umol/L) | Standard Deviation 0.1269 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 22 | 1.424 micromole/Liter (umol/L) | Standard Deviation 0.1036 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 43 | 1.433 micromole/Liter (umol/L) | Standard Deviation 0.2263 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 3 | 1.152 micromole/Liter (umol/L) | Standard Deviation 0.0719 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 1 | 1.677 micromole/Liter (umol/L) | Standard Deviation 0.6197 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 75 | 1.496 micromole/Liter (umol/L) | Standard Deviation 0.1576 |
| Cohort 1- 5 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 36 | 1.417 micromole/Liter (umol/L) | Standard Deviation 0.1845 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 36 | 1.455 micromole/Liter (umol/L) | Standard Deviation 0.2036 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 43 | 1.418 micromole/Liter (umol/L) | Standard Deviation 0.2204 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 2 | 1.550 micromole/Liter (umol/L) | Standard Deviation 0.3407 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 1 | 1.783 micromole/Liter (umol/L) | Standard Deviation 0.5743 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 29 | 1.332 micromole/Liter (umol/L) | Standard Deviation 0.2834 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 5 | 1.265 micromole/Liter (umol/L) | Standard Deviation 0.2091 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 3 | 1.303 micromole/Liter (umol/L) | Standard Deviation 0.2728 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 8 | 1.257 micromole/Liter (umol/L) | Standard Deviation 0.2279 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 15 | 1.388 micromole/Liter (umol/L) | Standard Deviation 0.108 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 75 | 1.375 micromole/Liter (umol/L) | Standard Deviation 0.2001 |
| Cohort 2- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 22 | 1.356 micromole/Liter (umol/L) | Standard Deviation 0.1195 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 22 | 1.350 micromole/Liter (umol/L) | Standard Deviation 0.2692 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 15 | 1.198 micromole/Liter (umol/L) | Standard Deviation 0.1982 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 2 | 0.915 micromole/Liter (umol/L) | Standard Deviation 0.2219 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 1 | 1.580 micromole/Liter (umol/L) | Standard Deviation 0.227 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 43 | 1.553 micromole/Liter (umol/L) | Standard Deviation 0.3434 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 3 | 0.950 micromole/Liter (umol/L) | Standard Deviation 0.2134 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 36 | 1.412 micromole/Liter (umol/L) | Standard Deviation 0.2226 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 5 | 0.978 micromole/Liter (umol/L) | Standard Deviation 0.2481 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 75 | 1.592 micromole/Liter (umol/L) | Standard Deviation 0.354 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 29 | 1.320 micromole/Liter (umol/L) | Standard Deviation 0.1582 |
| Cohort 3- 15 mg IV | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 8 | 1.177 micromole/Liter (umol/L) | Standard Deviation 0.3393 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 15 | 1.483 micromole/Liter (umol/L) | Standard Deviation 0.2817 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 1 | 1.683 micromole/Liter (umol/L) | Standard Deviation 0.2788 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 2 | 1.582 micromole/Liter (umol/L) | Standard Deviation 0.3579 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 3 | 1.405 micromole/Liter (umol/L) | Standard Deviation 0.1733 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 5 | 1.476 micromole/Liter (umol/L) | Standard Deviation 0.473 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 8 | 1.470 micromole/Liter (umol/L) | Standard Deviation 0.2206 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 22 | 1.558 micromole/Liter (umol/L) | Standard Deviation 0.1855 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 29 | 1.518 micromole/Liter (umol/L) | Standard Deviation 0.0952 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 36 | 1.516 micromole/Liter (umol/L) | Standard Deviation 0.2192 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 43 | 1.615 micromole/Liter (umol/L) | Standard Deviation 0.1463 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 75 | 1.820 micromole/Liter (umol/L) | Standard Deviation 0.0424 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 8 | 0.974 micromole/Liter (umol/L) | Standard Deviation 0.1218 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 1 | 1.577 micromole/Liter (umol/L) | Standard Deviation 0.2518 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 22 | 1.134 micromole/Liter (umol/L) | Standard Deviation 0.1828 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 5 | 0.962 micromole/Liter (umol/L) | Standard Deviation 0.2212 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 29 | 1.294 micromole/Liter (umol/L) | Standard Deviation 0.1997 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 3 | 1.093 micromole/Liter (umol/L) | Standard Deviation 0.3075 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 75 | 1.495 micromole/Liter (umol/L) | Standard Deviation 0.2073 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 36 | 1.308 micromole/Liter (umol/L) | Standard Deviation 0.176 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 2 | 1.165 micromole/Liter (umol/L) | Standard Deviation 0.2696 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 43 | 1.377 micromole/Liter (umol/L) | Standard Deviation 0.2673 |
| Cohort 5- 45 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 15 | 0.977 micromole/Liter (umol/L) | Standard Deviation 0.1695 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 29 | 1.044 micromole/Liter (umol/L) | Standard Deviation 0.179 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 3 | 0.778 micromole/Liter (umol/L) | Standard Deviation 0.0694 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 1 | 1.525 micromole/Liter (umol/L) | Standard Deviation 0.2882 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 8 | 0.750 micromole/Liter (umol/L) | Standard Deviation 0 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 15 | 0.830 micromole/Liter (umol/L) | Standard Deviation 0.1171 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 36 | 1.180 micromole/Liter (umol/L) | Standard Deviation 0.2347 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 2 | 0.823 micromole/Liter (umol/L) | Standard Deviation 0.1152 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 75 | 1.527 micromole/Liter (umol/L) | Standard Deviation 0.2527 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 43 | 1.243 micromole/Liter (umol/L) | Standard Deviation 0.3406 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 22 | 0.875 micromole/Liter (umol/L) | Standard Deviation 0.1524 |
| Cohort 6- 135 mg | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 5 | 0.750 micromole/Liter (umol/L) | Standard Deviation 0.75 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 43 | 1.225 micromole/Liter (umol/L) | Standard Deviation 0.1939 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 3 | 1.408 micromole/Liter (umol/L) | Standard Deviation 0.2405 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 8 | 1.368 micromole/Liter (umol/L) | Standard Deviation 0.32 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 75 | 1.290 micromole/Liter (umol/L) | Standard Deviation 0.1968 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 1 | 1.638 micromole/Liter (umol/L) | Standard Deviation 0.386 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 22 | 1.328 micromole/Liter (umol/L) | Standard Deviation 0.1873 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 5 | 1.509 micromole/Liter (umol/L) | Standard Deviation 0.4246 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 36 | 1.413 micromole/Liter (umol/L) | Standard Deviation 0.2283 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 2 | 1.418 micromole/Liter (umol/L) | Standard Deviation 0.2699 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 29 | 1.438 micromole/Liter (umol/L) | Standard Deviation 0.2677 |
| Pooled Placebo | Plasma Concentration of Inorganic Pyrophosphate (PPi) | Day 15 | 1.261 micromole/Liter (umol/L) | Standard Deviation 0.1614 |
Secondary
Plasma Concentration of Pyridoxal 5-Phosphate (PLP)
The plasma concentrations of PLP was assessed.
Time frame: Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PD profile of ALXN1910 can be adequately characterized were included in the PD Set. Here, Number Analyzed refers to the number of participants available for the specific Outcome measure for specific timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 5 | 8.597 nanogram/milliliter (ng/ml) | Standard Deviation 3.5325 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 2 | 7.593 nanogram/milliliter (ng/ml) | Standard Deviation 2.3404 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 15 | 10.170 nanogram/milliliter (ng/ml) | Standard Deviation 5.1691 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 29 | 9.722 nanogram/milliliter (ng/ml) | Standard Deviation 2.8996 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 8 | 8.753 nanogram/milliliter (ng/ml) | Standard Deviation 3.4828 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 22 | 13.656 nanogram/milliliter (ng/ml) | Standard Deviation 14.9897 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 43 | 10.597 nanogram/milliliter (ng/ml) | Standard Deviation 4.7562 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 3 | 8.148 nanogram/milliliter (ng/ml) | Standard Deviation 2.2653 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 1 | 10.187 nanogram/milliliter (ng/ml) | Standard Deviation 4.6534 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 75 | 12.284 nanogram/milliliter (ng/ml) | Standard Deviation 4.3254 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 36 | 11.115 nanogram/milliliter (ng/ml) | Standard Deviation 4.5799 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 36 | 7.932 nanogram/milliliter (ng/ml) | Standard Deviation 2.65 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 43 | 8.697 nanogram/milliliter (ng/ml) | Standard Deviation 3.6949 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 2 | 9.150 nanogram/milliliter (ng/ml) | Standard Deviation 3.5081 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 1 | 10.332 nanogram/milliliter (ng/ml) | Standard Deviation 3.5662 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 29 | 8.758 nanogram/milliliter (ng/ml) | Standard Deviation 4.4855 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 5 | 9.158 nanogram/milliliter (ng/ml) | Standard Deviation 3.4736 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 3 | 9.398 nanogram/milliliter (ng/ml) | Standard Deviation 3.3232 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 8 | 9.443 nanogram/milliliter (ng/ml) | Standard Deviation 2.971 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 15 | 8.360 nanogram/milliliter (ng/ml) | Standard Deviation 2.5086 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 75 | 9.620 nanogram/milliliter (ng/ml) | Standard Deviation 5.6757 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 22 | 8.384 nanogram/milliliter (ng/ml) | Standard Deviation 2.6076 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 22 | 9.805 nanogram/milliliter (ng/ml) | Standard Deviation 7.146 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 15 | 8.800 nanogram/milliliter (ng/ml) | Standard Deviation 5.7621 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 2 | 6.532 nanogram/milliliter (ng/ml) | Standard Deviation 2.5528 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 1 | 9.817 nanogram/milliliter (ng/ml) | Standard Deviation 4.8904 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 43 | 8.577 nanogram/milliliter (ng/ml) | Standard Deviation 3.3439 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 3 | 7.110 nanogram/milliliter (ng/ml) | Standard Deviation 2.4781 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 36 | 8.118 nanogram/milliliter (ng/ml) | Standard Deviation 3.6145 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 5 | 7.038 nanogram/milliliter (ng/ml) | Standard Deviation 2.0301 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 75 | 10.010 nanogram/milliliter (ng/ml) | Standard Deviation 4.9121 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 29 | 8.610 nanogram/milliliter (ng/ml) | Standard Deviation 2.6303 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 8 | 8.190 nanogram/milliliter (ng/ml) | Standard Deviation 5.6565 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 15 | 18.927 nanogram/milliliter (ng/ml) | Standard Deviation 11.9441 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 1 | 15.883 nanogram/milliliter (ng/ml) | Standard Deviation 5.7614 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 2 | 11.777 nanogram/milliliter (ng/ml) | Standard Deviation 4.286 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 3 | 11.487 nanogram/milliliter (ng/ml) | Standard Deviation 4.1591 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 5 | 10.098 nanogram/milliliter (ng/ml) | Standard Deviation 1.6344 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 8 | 10.572 nanogram/milliliter (ng/ml) | Standard Deviation 3.8381 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 22 | 30.427 nanogram/milliliter (ng/ml) | Standard Deviation 22.524 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 29 | 26.354 nanogram/milliliter (ng/ml) | Standard Deviation 24.3632 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 36 | 19.608 nanogram/milliliter (ng/ml) | Standard Deviation 19.6025 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 43 | 22.367 nanogram/milliliter (ng/ml) | Standard Deviation 19.342 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 75 | 17.750 nanogram/milliliter (ng/ml) | Standard Deviation 18.0312 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 8 | 7.562 nanogram/milliliter (ng/ml) | Standard Deviation 2.7438 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 1 | 11.503 nanogram/milliliter (ng/ml) | Standard Deviation 6.2856 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 22 | 10.828 nanogram/milliliter (ng/ml) | Standard Deviation 4.5559 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 5 | 7.672 nanogram/milliliter (ng/ml) | Standard Deviation 3.2028 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 29 | 14.880 nanogram/milliliter (ng/ml) | Standard Deviation 10.5484 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 3 | 8.182 nanogram/milliliter (ng/ml) | Standard Deviation 3.6379 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 75 | 14.918 nanogram/milliliter (ng/ml) | Standard Deviation 8.7744 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 36 | 18.514 nanogram/milliliter (ng/ml) | Standard Deviation 12.7452 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 2 | 10.552 nanogram/milliliter (ng/ml) | Standard Deviation 5.1884 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 43 | 16.223 nanogram/milliliter (ng/ml) | Standard Deviation 14.2766 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 15 | 9.292 nanogram/milliliter (ng/ml) | Standard Deviation 4.7827 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 29 | 12.682 nanogram/milliliter (ng/ml) | Standard Deviation 7.7458 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 3 | 5.737 nanogram/milliliter (ng/ml) | Standard Deviation 1.1692 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 1 | 13.940 nanogram/milliliter (ng/ml) | Standard Deviation 4.5167 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 8 | 5.270 nanogram/milliliter (ng/ml) | Standard Deviation 0.6037 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 15 | 10.040 nanogram/milliliter (ng/ml) | Standard Deviation 5.4156 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 36 | 12.318 nanogram/milliliter (ng/ml) | Standard Deviation 3.433 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 2 | 6.508 nanogram/milliliter (ng/ml) | Standard Deviation 1.6985 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 75 | 15.292 nanogram/milliliter (ng/ml) | Standard Deviation 6.7615 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 43 | 9.033 nanogram/milliliter (ng/ml) | Standard Deviation 2.5026 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 22 | 10.380 nanogram/milliliter (ng/ml) | Standard Deviation 8.4672 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 5 | 5.490 nanogram/milliliter (ng/ml) | Standard Deviation 1.2002 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 43 | 10.026 nanogram/milliliter (ng/ml) | Standard Deviation 5.6783 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 3 | 8.753 nanogram/milliliter (ng/ml) | Standard Deviation 4.0128 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 8 | 8.960 nanogram/milliliter (ng/ml) | Standard Deviation 4.4173 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 75 | 13.228 nanogram/milliliter (ng/ml) | Standard Deviation 13.3117 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 1 | 8.789 nanogram/milliliter (ng/ml) | Standard Deviation 3.8742 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 22 | 20.086 nanogram/milliliter (ng/ml) | Standard Deviation 26.9065 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 5 | 8.942 nanogram/milliliter (ng/ml) | Standard Deviation 5.087 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 36 | 14.191 nanogram/milliliter (ng/ml) | Standard Deviation 15.8284 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 2 | 8.356 nanogram/milliliter (ng/ml) | Standard Deviation 3.8675 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 29 | 16.309 nanogram/milliliter (ng/ml) | Standard Deviation 21.8318 |
| Pooled Placebo | Plasma Concentration of Pyridoxal 5-Phosphate (PLP) | Day 15 | 10.328 nanogram/milliliter (ng/ml) | Standard Deviation 7.0041 |
Secondary
Plasma Concentration of Pyridoxal (PL)
The plasma concentrations of PL was assessed.
Time frame: Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PD profile of ALXN1910 can be adequately characterized were included in the PD Set. Here, Number Analyzed refers to the number of participants available for the specific Outcome measure for specific timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 5 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 75 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 1 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 2 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 29 | 2.012 nanogram/milliliter (ng/ml) | Standard Deviation 0.0286 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 8 | 2.035 nanogram/milliliter (ng/ml) | Standard Deviation 0.0857 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 22 | 6.230 nanogram/milliliter (ng/ml) | Standard Deviation 8.9909 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 15 | 2.108 nanogram/milliliter (ng/ml) | Standard Deviation 0.1855 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 43 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 3 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxal (PL) | Day 36 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 1 | 2.133 nanogram/milliliter (ng/ml) | Standard Deviation 0.3266 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 5 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 22 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 43 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 75 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0.07 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 29 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 36 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 3 | 2.088 nanogram/milliliter (ng/ml) | Standard Deviation 0.1412 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 8 | 2.025 nanogram/milliliter (ng/ml) | Standard Deviation 0.0612 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 2 | 2.078 nanogram/milliliter (ng/ml) | Standard Deviation 0.1919 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 15 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 75 | 4.033 nanogram/milliliter (ng/ml) | Standard Deviation 4.9806 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 15 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 2 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 43 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 3 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 1 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 36 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 5 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 29 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 8 | 2.135 nanogram/milliliter (ng/ml) | Standard Deviation 0.3307 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxal (PL) | Day 22 | 2.017 nanogram/milliliter (ng/ml) | Standard Deviation 0.0408 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 15 | 2.850 nanogram/milliliter (ng/ml) | Standard Deviation 1.6067 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 1 | 2.092 nanogram/milliliter (ng/ml) | Standard Deviation 0.2245 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 2 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 3 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 5 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 8 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 22 | 5.042 nanogram/milliliter (ng/ml) | Standard Deviation 5.0662 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 29 | 3.524 nanogram/milliliter (ng/ml) | Standard Deviation 2.8236 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 36 | 3.783 nanogram/milliliter (ng/ml) | Standard Deviation 3.565 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 43 | 4.368 nanogram/milliliter (ng/ml) | Standard Deviation 4.8417 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxal (PL) | Day 75 | 3.305 nanogram/milliliter (ng/ml) | Standard Deviation 1.8455 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 8 | 3.903 nanogram/milliliter (ng/ml) | Standard Deviation 4.6037 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 1 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 22 | 2.140 nanogram/milliliter (ng/ml) | Standard Deviation 0.2706 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 5 | 2.015 nanogram/milliliter (ng/ml) | Standard Deviation 0.0367 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 29 | 2.652 nanogram/milliliter (ng/ml) | Standard Deviation 1.4579 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 3 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 75 | 2.498 nanogram/milliliter (ng/ml) | Standard Deviation 0.9561 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 36 | 2.732 nanogram/milliliter (ng/ml) | Standard Deviation 1.5382 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 2 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 43 | 2.797 nanogram/milliliter (ng/ml) | Standard Deviation 1.9368 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxal (PL) | Day 15 | 3.877 nanogram/milliliter (ng/ml) | Standard Deviation 4.1356 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 29 | 2.366 nanogram/milliliter (ng/ml) | Standard Deviation 0.7119 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 3 | 2.280 nanogram/milliliter (ng/ml) | Standard Deviation 0.5295 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 1 | 2.182 nanogram/milliliter (ng/ml) | Standard Deviation 0.3561 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 8 | 2.028 nanogram/milliliter (ng/ml) | Standard Deviation 0.0626 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 15 | 3.430 nanogram/milliliter (ng/ml) | Standard Deviation 2.7195 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 36 | 2.303 nanogram/milliliter (ng/ml) | Standard Deviation 0.3774 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 2 | 2.395 nanogram/milliliter (ng/ml) | Standard Deviation 0.6874 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 75 | 2.580 nanogram/milliliter (ng/ml) | Standard Deviation 0.7991 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 43 | 2.052 nanogram/milliliter (ng/ml) | Standard Deviation 0.0816 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 22 | 2.725 nanogram/milliliter (ng/ml) | Standard Deviation 1.6564 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxal (PL) | Day 5 | 2.157 nanogram/milliliter (ng/ml) | Standard Deviation 0.3552 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 43 | 2.119 nanogram/milliliter (ng/ml) | Standard Deviation 0.2683 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 3 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 8 | 2.014 nanogram/milliliter (ng/ml) | Standard Deviation 0.0491 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 75 | 2.525 nanogram/milliliter (ng/ml) | Standard Deviation 1.6742 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 1 | 2.003 nanogram/milliliter (ng/ml) | Standard Deviation 0.0087 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 22 | 3.904 nanogram/milliliter (ng/ml) | Standard Deviation 4.909 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 5 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 36 | 3.264 nanogram/milliliter (ng/ml) | Standard Deviation 4.191 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 2 | 2.000 nanogram/milliliter (ng/ml) | Standard Deviation 0 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 29 | 3.922 nanogram/milliliter (ng/ml) | Standard Deviation 4.4773 |
| Pooled Placebo | Plasma Concentration of Pyridoxal (PL) | Day 15 | 2.183 nanogram/milliliter (ng/ml) | Standard Deviation 0.6319 |
Secondary
Plasma Concentration of Pyridoxic Acid (PA)
The plasma concentrations of PA was assessed.
Time frame: Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PD profile of ALXN1910 can be adequately characterized were included in the PD Set. Here, Number Analyzed refers to the number of participants available for the specific Outcome measure for specific timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 8 | 2.680 nanogram/milliliter (ng/ml) | Standard Deviation 1.5016 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 5 | 2.517 nanogram/milliliter (ng/ml) | Standard Deviation 0.4942 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 75 | 3.620 nanogram/milliliter (ng/ml) | Standard Deviation 1.2921 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 43 | 2.415 nanogram/milliliter (ng/ml) | Standard Deviation 0.5445 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 2 | 2.270 nanogram/milliliter (ng/ml) | Standard Deviation 0.5563 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 1 | 2.613 nanogram/milliliter (ng/ml) | Standard Deviation 0.8986 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 36 | 2.833 nanogram/milliliter (ng/ml) | Standard Deviation 1.1429 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 29 | 3.453 nanogram/milliliter (ng/ml) | Standard Deviation 1.0153 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 3 | 2.273 nanogram/milliliter (ng/ml) | Standard Deviation 0.3469 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 22 | 10.750 nanogram/milliliter (ng/ml) | Standard Deviation 18.8695 |
| Cohort 1- 5 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 15 | 2.812 nanogram/milliliter (ng/ml) | Standard Deviation 0.942 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 15 | 3.000 nanogram/milliliter (ng/ml) | Standard Deviation 1.0794 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 3 | 2.828 nanogram/milliliter (ng/ml) | Standard Deviation 0.598 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 5 | 2.782 nanogram/milliliter (ng/ml) | Standard Deviation 0.5094 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 1 | 3.088 nanogram/milliliter (ng/ml) | Standard Deviation 0.5566 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 75 | 2.998 nanogram/milliliter (ng/ml) | Standard Deviation 0.9216 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 29 | 2.575 nanogram/milliliter (ng/ml) | Standard Deviation 0.6291 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 43 | 2.827 nanogram/milliliter (ng/ml) | Standard Deviation 0.8977 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 8 | 2.797 nanogram/milliliter (ng/ml) | Standard Deviation 1.0017 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 36 | 2.657 nanogram/milliliter (ng/ml) | Standard Deviation 0.7266 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 22 | 2.566 nanogram/milliliter (ng/ml) | Standard Deviation 0.6971 |
| Cohort 2- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 2 | 2.502 nanogram/milliliter (ng/ml) | Standard Deviation 0.3333 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 3 | 2.558 nanogram/milliliter (ng/ml) | Standard Deviation 0.6787 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 1 | 2.988 nanogram/milliliter (ng/ml) | Standard Deviation 1.054 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 2 | 2.580 nanogram/milliliter (ng/ml) | Standard Deviation 0.6935 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 5 | 2.702 nanogram/milliliter (ng/ml) | Standard Deviation 0.5883 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 8 | 2.733 nanogram/milliliter (ng/ml) | Standard Deviation 0.8122 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 15 | 2.908 nanogram/milliliter (ng/ml) | Standard Deviation 0.9542 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 22 | 3.172 nanogram/milliliter (ng/ml) | Standard Deviation 1.8925 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 29 | 3.070 nanogram/milliliter (ng/ml) | Standard Deviation 1.0623 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 36 | 2.563 nanogram/milliliter (ng/ml) | Standard Deviation 1.1121 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 43 | 3.330 nanogram/milliliter (ng/ml) | Standard Deviation 1.9655 |
| Cohort 3- 15 mg IV | Plasma Concentration of Pyridoxic Acid (PA) | Day 75 | 2.868 nanogram/milliliter (ng/ml) | Standard Deviation 0.7116 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 1 | 3.590 nanogram/milliliter (ng/ml) | Standard Deviation 1.8724 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 2 | 3.140 nanogram/milliliter (ng/ml) | Standard Deviation 1.4506 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 29 | 6.922 nanogram/milliliter (ng/ml) | Standard Deviation 7.2945 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 22 | 10.143 nanogram/milliliter (ng/ml) | Standard Deviation 11.4645 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 3 | 3.240 nanogram/milliliter (ng/ml) | Standard Deviation 1.1469 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 75 | 6.350 nanogram/milliliter (ng/ml) | Standard Deviation 6.1518 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 5 | 3.070 nanogram/milliliter (ng/ml) | Standard Deviation 0.9821 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 15 | 5.132 nanogram/milliliter (ng/ml) | Standard Deviation 3.4143 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 8 | 3.497 nanogram/milliliter (ng/ml) | Standard Deviation 1.6013 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 43 | 8.055 nanogram/milliliter (ng/ml) | Standard Deviation 8.7461 |
| Japanese Cohort 4- 15 mg SC | Plasma Concentration of Pyridoxic Acid (PA) | Day 36 | 6.185 nanogram/milliliter (ng/ml) | Standard Deviation 7.3577 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 5 | 2.605 nanogram/milliliter (ng/ml) | Standard Deviation 0.5392 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 8 | 3.012 nanogram/milliliter (ng/ml) | Standard Deviation 1.1908 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 3 | 2.463 nanogram/milliliter (ng/ml) | Standard Deviation 0.5376 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 15 | 3.285 nanogram/milliliter (ng/ml) | Standard Deviation 1.7404 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 43 | 4.123 nanogram/milliliter (ng/ml) | Standard Deviation 3.3854 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 22 | 3.946 nanogram/milliliter (ng/ml) | Standard Deviation 1.963 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 2 | 2.680 nanogram/milliliter (ng/ml) | Standard Deviation 0.7706 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 29 | 4.576 nanogram/milliliter (ng/ml) | Standard Deviation 3.49 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 75 | 3.595 nanogram/milliliter (ng/ml) | Standard Deviation 1.8915 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 36 | 4.236 nanogram/milliliter (ng/ml) | Standard Deviation 2.7877 |
| Cohort 5- 45 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 1 | 2.750 nanogram/milliliter (ng/ml) | Standard Deviation 0.8456 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 8 | 3.054 nanogram/milliliter (ng/ml) | Standard Deviation 0.4078 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 75 | 4.580 nanogram/milliliter (ng/ml) | Standard Deviation 1.1087 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 15 | 6.118 nanogram/milliliter (ng/ml) | Standard Deviation 5.576 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 3 | 2.828 nanogram/milliliter (ng/ml) | Standard Deviation 0.8422 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 43 | 3.220 nanogram/milliliter (ng/ml) | Standard Deviation 0.8897 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 36 | 3.950 nanogram/milliliter (ng/ml) | Standard Deviation 1.6757 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 29 | 4.482 nanogram/milliliter (ng/ml) | Standard Deviation 2.3754 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 2 | 2.955 nanogram/milliliter (ng/ml) | Standard Deviation 0.9038 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 5 | 3.125 nanogram/milliliter (ng/ml) | Standard Deviation 0.3094 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 22 | 4.532 nanogram/milliliter (ng/ml) | Standard Deviation 2.0736 |
| Cohort 6- 135 mg | Plasma Concentration of Pyridoxic Acid (PA) | Day 1 | 3.797 nanogram/milliliter (ng/ml) | Standard Deviation 1.3833 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 75 | 3.695 nanogram/milliliter (ng/ml) | Standard Deviation 2.7428 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 29 | 4.553 nanogram/milliliter (ng/ml) | Standard Deviation 4.6084 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 2 | 2.541 nanogram/milliliter (ng/ml) | Standard Deviation 0.5817 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 1 | 2.798 nanogram/milliliter (ng/ml) | Standard Deviation 0.7626 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 3 | 2.751 nanogram/milliliter (ng/ml) | Standard Deviation 0.6523 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 15 | 2.930 nanogram/milliliter (ng/ml) | Standard Deviation 1.4804 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 36 | 4.557 nanogram/milliliter (ng/ml) | Standard Deviation 4.8259 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 43 | 3.328 nanogram/milliliter (ng/ml) | Standard Deviation 1.4716 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 8 | 2.939 nanogram/milliliter (ng/ml) | Standard Deviation 0.8534 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 22 | 5.579 nanogram/milliliter (ng/ml) | Standard Deviation 7.2517 |
| Pooled Placebo | Plasma Concentration of Pyridoxic Acid (PA) | Day 5 | 2.713 nanogram/milliliter (ng/ml) | Standard Deviation 0.5881 |
Secondary
Terminal-phase Elimination Rate Constant (λz)
The λz was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number of Participants Analyzed refers to the number of participants available for the specific Outcome measure for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | Terminal-phase Elimination Rate Constant (λz) | 0.004172 1/hour (1/h) | Geometric Coefficient of Variation 25.1 |
| Cohort 2- 15 mg SC | Terminal-phase Elimination Rate Constant (λz) | 0.003222 1/hour (1/h) | Geometric Coefficient of Variation 12.2 |
| Cohort 3- 15 mg IV | Terminal-phase Elimination Rate Constant (λz) | 0.003556 1/hour (1/h) | Geometric Coefficient of Variation 19.2 |
| Japanese Cohort 4- 15 mg SC | Terminal-phase Elimination Rate Constant (λz) | 0.003341 1/hour (1/h) | Geometric Coefficient of Variation 13.9 |
| Cohort 5- 45 mg | Terminal-phase Elimination Rate Constant (λz) | 0.002555 1/hour (1/h) | Geometric Coefficient of Variation 6 |
| Cohort 6- 135 mg | Terminal-phase Elimination Rate Constant (λz) | 0.002631 1/hour (1/h) | Geometric Coefficient of Variation 18.8 |
Secondary
Time to Maximum Observed Serum Concentration (Tmax)
The Tmax was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1- 5 mg | Time to Maximum Observed Serum Concentration (Tmax) | 0.48 hour (h) |
| Cohort 2- 15 mg SC | Time to Maximum Observed Serum Concentration (Tmax) | 107.85 hour (h) |
| Cohort 3- 15 mg IV | Time to Maximum Observed Serum Concentration (Tmax) | 0.52 hour (h) |
| Japanese Cohort 4- 15 mg SC | Time to Maximum Observed Serum Concentration (Tmax) | 108.02 hour (h) |
| Cohort 5- 45 mg | Time to Maximum Observed Serum Concentration (Tmax) | 95.99 hour (h) |
| Cohort 6- 135 mg | Time to Maximum Observed Serum Concentration (Tmax) | 84.14 hour (h) |
Secondary
Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F)
The CL or CL/F was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number of Participants Analyzed refers to the number of participants available for the specific Outcome measure for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F) | 0.05591 Liter/hour (L/h) | Geometric Coefficient of Variation 22.2 |
| Cohort 2- 15 mg SC | Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F) | 0.08926 Liter/hour (L/h) | Geometric Coefficient of Variation 20.3 |
| Cohort 3- 15 mg IV | Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F) | 0.06135 Liter/hour (L/h) | Geometric Coefficient of Variation 13.8 |
| Japanese Cohort 4- 15 mg SC | Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F) | 0.09507 Liter/hour (L/h) | Geometric Coefficient of Variation 23.4 |
| Cohort 5- 45 mg | Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F) | 0.08691 Liter/hour (L/h) | Geometric Coefficient of Variation 12.4 |
| Cohort 6- 135 mg | Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F) | 0.07945 Liter/hour (L/h) | Geometric Coefficient of Variation 19.8 |
Secondary
Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F)
The Vd or Vd/F was assed as PK parameter of single ascending doses of ALXN1910.
Time frame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
Population: All treated participants for whom the PK profile of ALXN1910 can be adequately characterized were included in the PK Set. PK analyses were based upon the study intervention received. Here, Number of Participants Analyzed refers to the number of participants available for the specific Outcome measure for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- 5 mg | Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F) | 12.56 Liter (L) | Geometric Coefficient of Variation 11.2 |
| Cohort 2- 15 mg SC | Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F) | 27.12 Liter (L) | Geometric Coefficient of Variation 29.4 |
| Cohort 3- 15 mg IV | Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F) | 17.25 Liter (L) | Geometric Coefficient of Variation 12.1 |
| Japanese Cohort 4- 15 mg SC | Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F) | 28.46 Liter (L) | Geometric Coefficient of Variation 21 |
| Cohort 5- 45 mg | Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F) | 34.02 Liter (L) | Geometric Coefficient of Variation 11.3 |
| Cohort 6- 135 mg | Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F) | 30.20 Liter (L) | Geometric Coefficient of Variation 29.3 |