A Study to Assess the Safety and Tolerability, Including Gastrointestinal Safety, Pharmacokinetics and Pharmacodynamics of ASP7657 in Caucasian Healthy Male and Female Subjects

NCT02108548 | Terminated Phase 1

• 2 other identifiers: 7657-CL-00012013-004357-25
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of single and multiple ascending oral doses of ASP7657 in healthy subjects.

Conditions

Pharmacokinetics of ASP7657; Pharmacodynamics of ASP7657; Healthy Subjects

Keywords

ASP7657; Pharmacokinetics; Pharmacodynamics; Healthy Subjects; First in man; Safety

Outcome Measures

Primary Outcomes (1)

• Part 1 and 2: Safety assessed by adverse events, vital signs, laboratory tests, electrocardiogram (ECGs), collagen and adenosine diphosphate (ADP)-induced platelet aggregation, and gastrointestinal (GI) safety assessments (Part 2 only)

  Up to Day 20

Secondary Outcomes (10)

• Part 1: Pharmacokinetics (PK) profile of ASP7657 after a single dose in plasma: AUCinf, AUClast, tlag, tmax, Cmax, t 1/2, Vz/F, CL/F

  Day 1

• Part 1: PK profile of ASP7657 in urine: Aelast, Aeinf, Aelast%, Aeinf%, CLr

  Day 1

• Part 1: Pharmacodynamics (PD) profile of tumor necrosis factor alpha (TNF-α) in whole blood: maximum response (Rmax), area under the dose-response curve (AURC), and time to reach maximum response (tmax,R)

  Day 1

• Part 1: PD in urine: Total urine volume over 24 hours

  Day -1 and Day 1

• Part 2: PK profile of ASP7657 after first dose in plasma: tlag, tmax, Cmax and AUC from the time of dosing to 24 hours postdose (AUC24)

  Day 1

Study Arms (7)

Part 1: ASP7657 Single Ascending Dose

EXPERIMENTAL

Drug: ASP7657

Part 1: ASP7657 Single Ascending Dose - Food Effect

EXPERIMENTAL

Drug: ASP7657

Part 1: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Part 2: ASP7657 Multiple Ascending Dose

EXPERIMENTAL

Drug: ASP7657

Part 2: ASP7657 Multiple Ascending Dose Elderly

EXPERIMENTAL

Drug: ASP7657

Part 2: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Part 2: Naproxen

ACTIVE COMPARATOR

Drug: naproxen

Interventions

ASP7657 DRUG

oral

Part 1: ASP7657 Single Ascending Dose; Part 1: ASP7657 Single Ascending Dose - Food Effect; Part 2: ASP7657 Multiple Ascending Dose; Part 2: ASP7657 Multiple Ascending Dose Elderly

Placebo DRUG

oral

Part 1: Placebo; Part 2: Placebo

naproxen DRUG

oral

Part 2: Naproxen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a body mass index (BMI) range of 18.5 to 30.0 kg/m2, inclusive. The subject weighs at least 50 kg \[screening\]
• Subject agrees to undergo gastro-duodenoscopy (GDS) if needed (Part 1: in case of gastrointestinal (GI) complaints/positive fecal blood test; Part 2: all subjects)

You may not qualify if:

• Subject has known or suspected hypersensitivity to ASP7657 or naproxen, or any components of the formulation used
• Subject has any of the liver function test above the upper limit of normal (ULN)
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
• Subject has any history or evidence of any clinically significant cardiovascular, GI, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to day of admission
• Subject has any clinically significant abnormality
• Subject has a pulse \< 40 or \> 90 beats per minute (bpm); mean systolic blood pressure (SBP) \> 140 mmHg; mean diastolic blood pressure (DBP) \> 90 mmHg (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) at day -1. (For elderly subjects the following criteria apply: DBP \> 100 mmHg, SBP \> 160 mmHg \[day of admission\])
• Subject has a mean QT interval corrected for heart rate using Fridericia's formula (QTc(F)) of \> 430 ms (for males) and \> 450 ms (for females).
• Subject uses any prescribed or nonprescribed drugs (including nonsteroidal anti-inflammatory drugs (NSAIDs), anti-coagulants, vitamins, natural and herbal remedies, e.g., St. John's wort) in the 2 weeks prior to first study drug administration, except for occasional use of paracetamol (up to 2 g/day)
• Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit.
• Subject has a history of drinking \> 21 units (males) or \> 14 units (females) of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer \[5%\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) within 3 months prior to admission to the clinical unit or the subject tests positive at screening or clinical admission for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates)
• Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit
• Subject has 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 clinic admission
• Subject uses any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to admission to the clinical unit regularly
• Subject has a positive serology test for hepatitis B surface antigen (HBsAg), anti-hepatitis A virus (HAV) (immunoglobulin \[Ig\]M), anti-hepatitis C virus (HCV) or anti-human immunodeficiency virus (HIV) 1+2

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Parexel Early Phase Clinical Unit

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

MeSH Terms

Interventions

ASP7657; Naproxen

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Medical Director

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2014
• First Posted: April 9, 2014
• Study Start: April 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 27, 2015

Record last verified: 2015-03

Locations

GB (1)