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A Study to Evaluate the Safety of ASP2408 After Subcutaneous Administration to Healthy Male Subjects

Phase 1
Completed
Conditions
Healthy
Pharmacokinetics of ASP2408
Interventions
Drug: Placebo
Registration Number
NCT02140125
Lead Sponsor
Astellas Pharma Inc
Brief Summary

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of single subcutaneous dose of ASP2408 in non-elderly healthy adult male subjects. The pharmacodynamics of ASP2408 is also being evaluated.

Detailed Description

This clinical study will be conducted as a double-blind, placebo-controlled, single ascending subcutaneous dose study. As shown in the table below, the study will be conducted using 3 cohorts, to which a total of 24 subjects will be randomly assigned (18 subjects receiving ASP2408 and 6 subjects receiving placebo). Each cohort will consist of 8 subjects, who will be randomly assigned to either the ASP2408 group or the placebo group at the ratio of 3 to 1.

Each subject will need to be hospitalized until Day 8 (start date of study drug administration will be regarded as Day 1) and will be observed until Day 90. The investigator or subinvestigator will carefully observe each subject for any sign or symptom of adverse events.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
24
Inclusion Criteria
  • BMI (at screening): ≥ 17.6 kg/m2, < 26.4 kg/m2
  • Healthy, as judged by the investigator or subinvestigator based on the results of medical examination (subjective symptoms and objective findings) and all tests obtained at screening and during the period from hospitalization (Day -2) to immediately before study drug administration
  • Subjects who agree to use effective contraception until 90 days after study drug administration
Exclusion Criteria
  • Received any investigational drugs in other clinical or post-marketing studies within 120 days before the study or is scheduled to receive any investigational drugs
  • Donated 400 mL of whole blood within 90 days before the study or during the period from the screening, 200 mL of whole blood within 30 days, or blood components within 14 days before the study, or is scheduled to donate 400 mL of whole blood or blood components
  • Received medication within 7 days before hospitalization (Day -2) or is scheduled to receive medication
  • Received systemic medications influencing immune functions (e.g., steroids, tacrolimus hydrate, anticancer drugs, and biological products) within 365 days before study drug administration
  • Received a live virus vaccine (e.g., BCG, polio, measles, and rubella) within 180 days before study drug administration, or cannot agree not to receive these vaccines for 180 days after study drug administration
  • Received a live virus vaccine (e.g., BCG, polio, measles, and rubella) within 180 days before study drug administration, or cannot agree not to receive these vaccines for 180 days after study drug administration
  • A deviation from the normal range of blood pressure, pulse rate, body temperature, or standard 12-lead ECG (see Table 3.3-1) at screening or the day before study drug administration (Day -1)
  • Any deviation of the normal ranges in laboratory tests before study drug administration
  • Failure to meet any criteria for standard 12-lead ECG for QT assessment at screening
  • A positive result for tuberculosis test
  • Concurrent or history of drug allergies, anaphylaxis, or severe allergic reaction
  • Upper GI disease
  • Concurrent or previous hepatic disease (e.g., viral hepatitis and drug-induced liver injury)
  • Concurrent or previous heart disease (e.g., congestive heart failure, angina pectoris, and arrhythmia requiring treatment)
  • Concurrent or previous respiratory disease (e.g., bronchial asthma and chronic bronchitis; except for a history of childhood asthma)
  • Previous operation of gut excision
  • Concurrent or previous renal disease (e.g., acute renal failure, glomerulonephritis, and interstitial nephritis; except for a history of calculus)
  • Concurrent or previous endocrine disease (e.g., hyperthyroid, abnormality of growth hormone)
  • Concurrent or previous cerebrovascular disorder (e.g., cerebral infarction)
  • Concurrent or previous malignant tumor
  • Concurrent or previous serious infection (e.g., sepsis, pneumonia requiring hospitalization, and pyelonephritis)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ASP2408 low dose groupASP2408-
ASP2408 middle dose groupASP2408-
ASP2408 high dose groupASP2408-
Placebo groupPlacebo-
Primary Outcome Measures
NameTimeMethod
Safety assessed by the incidence of adverse events, vital signs, lab tests, and 12-lead ECGUp to 90 days after administration
Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics of serum ASP2408On day-1, day-2, day-3, day-4, day-5, day-6, day-7, day-8, day-9, day-11, day-13, day-15, day-22, day-29 day-43, day-60 and day-90

The pharmacokinetic analysis employed non-compartmental methods using serum concentrations of ASP2408. The following pharmacokinetic parameters were estimated: AUCinf, AUClast, Cmax, CL/F, tmax, t1/2, and Vz/F.

CD80/CD86 receptor occupancyOn day-1, day-2, day-3, day-5, day-8, day 15, day-22, day-29 and day-90
Total lymphocyte countOn day-1, day-2, day-3, day-5, day-8, day 15, day-22, day-29 and day-90
Peripheral blood lymphocyte subsetOn day-1, day-2, day-3, day-5, day-8, day 15, day-22, day-29 and day-90
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