A Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP2408 Following Single Intravenous Doses in Healthy Subjects

Healthy Subjects Clinical Trial

Official title:

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP2408 Following Single Intravenous Doses in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02125435
• Other study ID #: 2408-CL-0101
• Status: Completed
• Phase: Phase 1
• First received: April 25, 2014
• Last updated: April 25, 2014
• Start date: January 2011
• Est. completion date: May 2012

Study information

• Verified date: April 2014
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of single ascending intravenous (IV) doses of ASP2408 in non-elderly, healthy male and female subjects and to evaluate the pharmacodynamics of ASP2408.

Description:

This is single-dose escalation study composed of 8 sequential cohorts of healthy subjects receiving increasing doses of intravenously administered ASP2408 or matching placebo. Subjects will be confined in the clinic for 8 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Subject weighs at least 50 kg, and has a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive.

• Results of subject's 12-lead electrocardiogram (ECG) are normal or, if abnormal, the abnormality is not clinically significant as determined by the investigator.

• Female subject must be at least two years postmenopausal OR surgically sterile (with documentation provided by a healthcare professional) and not pregnant or lactating.

• Male subject agrees to the use of male condoms until the end of study or 60 days post dose, whichever is longer.

• Subject is highly likely to comply with the protocol and complete the study.

Exclusion Criteria:

• Subject has a history of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy excluding adequately treated non-melanoma skin cancer.

• Subject has a history of severe allergic or anaphylactic reactions.

• Subject is a female of child-bearing potential.

• Subject has a history of consuming more than 14 units of alcoholic beverages per week or has a history of alcoholism or drug/chemical/ substance abuse within past 2 years (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits).

• Subject has a positive test for alcohol or drugs of abuse.

• Subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic check-in.

• Subject has a past history of opportunistic infection.

• Subject has a supine mean systolic blood pressure < 90 or > 160 mmHg and a mean diastolic blood pressure < 50 or > 90 mmHg, or mean pulse rate higher than 100 beats per min (bpm).

• Subject is known positive for human immunodeficiency virus (HIV) antibody.

• Subject has a positive TB skin test or Quantiferon Gold test or T-SPOT® test at Screening.

• Subject has a positive test for hepatitis C antibody, or positive test for hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody.

• Subject's laboratory test results:

• alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), are greater than 1.5 times the upper limit of normal

• are outside the normal limits and considered by the investigator to be clinically significant with regard to the remaining per-protocol laboratory tests.

• Subject received any vaccine within 60 days prior to study drug administration.

• Subject received any systemic immunosuppressant agent within 2 months prior to study drug administration.

• Subject has previously received any antibody or therapeutic biologic product prior to study drug administration.

• Subject received any systemic steroid within 2 months or steroid inhaler within 1 month prior to study drug administration.

• Subject has had treatment with prescription, non-prescription or complementary and alternative medicines (CAM) within 14 days prior to study drug administration.

• Subject has received an experimental agent within 30 days or five half-lives, whichever is longer, prior to study drug administration.

• Subject is participating in another clinical trial or has participated in another dose group of the current trial.

• Subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.

• Subject has a history of heavy smoking or has used tobacco-containing products and nicotine or nicotine-containing products in the past six months.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Subjects
• Pharmacokinetics of ASP2408

Intervention

Drug:
• ASP2408
intravenous
• Placebo
intravenous

Locations

Country	Name	City	State
United States	PAREXEL International	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameter of ASP2408:AUClast	Area Under the Concentration - Time curve from time 0 up to the last quantifiable concentration (AUClast)	Days 1-8, 15, 22, 29, 43, 60, 90	No
Primary	Pharmacokinetic parameter of ASP2408: AUCinf	Area Under the Concentration - Time curve from time 0 extrapolated to infinity (AUCinf)	Days 1 -8, 15, 22, 29, 43, 60, 90	No
Primary	Pharmacokinetic parameter of ASP2408:Cmax	Maximum concentration (Cmax)	Days 1-8, 15, 22, 29, 43, 60, 90	No
Primary	Safety assessed by adverse events, laboratory tests, immunoglobulin, 12-lead electrocardiograms (ECGs), vital signs and anti-2408 antibody formulation		up to 90 days	No
Secondary	Composite of pharmacokinetics of ASP2408: tmax, t1/2, Vz, CLtot	Time to attain Cmax (tmax), apparent terminal elimination half-life (t1/2), Terminal phase volume (Vz), Total Body Clearance (CLtot)	Days 1-8, 15, 22, 29, 43, 60, 90	No
Secondary	Pharmacodynamic parameters of ASP2408: CD80 and CD86 receptor occupancy		Days 1-3, 5, 8, 15, 22, 29, 43, 60, 90	No
Secondary	Total lymphocyte count		Days 1-3, 5, 8, 15, 22, 29, 43, 60, 90	No
Secondary	Peripheral lymphocyte subset quantification		Days 1-3, 5, 8, 15, 22, 29, 43, 60, 90	No