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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
48
Clinical Trial Site
Harrow, United Kingdom
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
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
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
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
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
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
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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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