A Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP015K in Healthy Subjects

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Randomized, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP015K Following Single Doses in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02141425
• Other study ID #: 015K-CL-HV07
• Status: Completed
• Phase: Phase 1
• First received: May 15, 2014
• Last updated: June 2, 2014
• Start date: March 2014
• Est. completion date: April 2014

Study information

• Verified date: June 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 purpose of this study is to assess the safety, tolerability and pharmacokinetics of single ascending doses of ASP015K.

Description:

Subjects will be enrolled in 1 of 3 dose cohorts (low, medium and high). Each cohort will consist of 8 subjects with a 3:1 randomization ratio for ASP015K to placebo. Subjects will be confined to the clinic for study procedures until day 4 (5 days). After all subjects in a dose cohort have completed study procedures through day 4, a decision will be made whether or not dosing and enrollment of the next dose cohort should occur, which will only take place after a review of the safety and tolerability data through day 4 of the most recent dose cohort and any additional reported adverse events (AEs) for previously dosed cohorts.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Female subject must be either:

• Of non-childbearing potential:

1. postmenopausal (defined as at least 1 year without any menses) prior to screening,

2. or documented surgically sterile or status post-hysterectomy (at least 1 month prior to screening).

• Or, if of childbearing potential:

1. must have a negative pregnancy test at screening and day -1.

2. must use highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and throughout the study period and for 90 days after final study drug administration.

• Female subject must not donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration.

• Male subject and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continuing throughout the study period, and for 90 days after final study drug administration.

• Male subject must not donate sperm starting at screening and continuing throughout the study period, and for 90 days after final study drug administration.

• Subject has a Body Mass Index (BMI) range of 18.5 to 32.0 kg/m2, inclusive, and must weigh at least 50 kg at screening.

• Subject must be capable of swallowing multiple (up to 20) tablets.

• Subject agrees not to participate in another investigational study while on treatment.

Exclusion Criteria:

• Female subject who has been pregnant within 6 months before screening assessment or breast feeding within 3 months before screening.

• Subject has a known or suspected hypersensitivity to ASP015K or any components of the formulations used.

• Subject has any of the liver function tests (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase or total bilirubin) above the ULN at screening or day -1. If the result is outside the limits, the assessment may be repeated once at screening and day -1.

• Subject has any clinically significant history of allergic conditions.

• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal (GI), endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy, as judged by the investigator or designee.

• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (non-cutaneous) infection within 1 week prior to day -1.

• Subject has any clinically significant abnormality following the investigator's review of the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or day -1.

• Subject has a mean pulse < 40 or > 90 beats per minute, mean systolic blood pressure (BP) > 140 mmHg or mean diastolic BP > 90 mmHg (measurements taken in triplicate after subject has been resting in sitting position for 5 minutes) at screening or day -1.

• Subject has a mean QTcF interval of > 430 msec (for males) and > 450 msec (for females) at screening or day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken. If this triplicate also gives an abnormal result, the subject should be excluded.

• Subject has used any prescribed or non-prescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to study drug administration, with the exception of hormone replacement therapy (HRT), hormonal contraceptives and intermittent acetaminophen (no more than 2g per day).

• Subject has smoked or has used tobacco-containing products and nicotine or nicotine-containing products in the past 6 months prior to screening.

• Subject has a history of consuming more than 14 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical substance abuse within the past 2 years prior to screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits).

• Subject has a positive test for alcohol, drugs of abuse or cotinine at screening or day -1.

• Subject anticipates an inability to abstain from xanthine (e.g., caffeine), grapefruit, Seville oranges (including marmalade), star fruit or any products containing these items from 72 hours prior to day -1 and throughout the duration of the study.

• Subject has used any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to day -1.

• Subject has had any significant blood loss, donated 1 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 day -1.

• Subject has a positive test for hepatitis B surface antigen, anti-hepatitis A virus (Immunoglobulin M) antibody, anti-hepatitis C virus antibody, hepatitis B core antibody or anti-human immunodeficiency virus Type 1 or Type 2 at screening.

• Subject has a positive tuberculosis skin test, Quantiferon Gold® or T-SPOT® test at screening.

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

• Subject has an absolute neutrophil count (ANC) < 2000 cells/mm3 or a creatine phosphokinase (CPK) > 1.5 x ULN at screening or day -1. If the result is outside the limits, the assessment may be repeated once at screening and day -1.

• Subject has had major GI surgery or has a medical condition that may inhibit the absorption and/or metabolism of study drug.

• Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half-lives of the drug, whichever is longer, prior to screening.

• Subject has any other condition, which in the opinion of the investigator, precludes the subject's participation in the study.

• Subject is an employee of the Astellas Group, Janssen Pharmaceuticals or vendors involved in the study.

• Subject has participated in a prior study with ASP015K.

Study Design

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

Related Conditions & MeSH terms

• Healthy Volunteers
• Pharmacokinetics of ASP015K

Intervention

Drug:
• ASP015K
oral
• Placebo
oral

Locations

Country	Name	City	State
United States	California Clinical Trials Medical Group/Parexel	Glendale	California

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Janssen Biotech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as assessed by adverse events, clinical laboratory tests, electrocardiogram (ECG) measurements, physical examination abnormalities and vital signs		Days 1-4	Yes
Secondary	Pharmacokinetic profile of ASP015K: Cmax, AUClast, AUCinf, tmax, t1/2, CL/F, Vz/F	Maximum Concentration (Cmax), Area Under the Plasma Concentration - Time Curve from Time Zero to Time of Last Measurable Concentration (AUClast), Area Under the Plasma concentration - Time Curve from Time Zero to Infinity (AUCinf), Time of Attain Cmax (tmax), Apparent Terminal Elimination Half-life (t1/2), Apparent total systemic clearance (CL/F), apparent volume of distribution (Vz/F)	Days 1-4	No
Secondary	Pharmacokinetic profile of ASP015K metabolites: Cmax, AUClast, AUCinf, tmax, t1/2		Days 1-4	No