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

Astellas

Status and phase: Terminated; Phase 1

Conditions: Pharmacodynamics of ASP7657; Pharmacokinetics of ASP7657; Healthy Subjects

Treatments: Drug: naproxen; Drug: Placebo; Drug: ASP7657

Study type: Interventional

Funder types: Industry

Identifiers

NCT02108548

7657-CL-0001

2013-004357-25 (EudraCT Number)

Details and patient eligibility

About

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

Full description

Subjects are healthy males aged 18 to 55 years of age (inclusive) (Parts 1 and 2, young cohorts) or the subject is an elderly healthy male or female subject aged 65 years or more (Part 2, elderly cohort).

Enrollment: 89 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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
• Subject has a positive H.Pylori test at screening
• Subject has a positive fecal blood test at screening
• Subject participated in any interventional clinical study or has been treated with any investigational drugs within 90 days or 5 half-lives whichever is longer, prior to the initiation of screening
• Subject is an employee of the Astellas Group or Clinical Research Organization involved in the study
• Subject has a history of peptic ulceration or significant dyspepsia
• Subject uses concomitant medication associated with peptic ulceration, or presence of other risk factors for peptic ulceration
• Subject, if non-elderly, has endoscopic evidence of inflammation, ulceration, erosion, mucosal hemorrhage, or active bleeding in esophagus, stomach, pyloric channel or duodenum, and a mucosal grading scale score > 2 for both stomach and duodenum at baseline visit (Part 2 healthy young male cohorts)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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89 participants in 7 patient groups, including a placebo group

Part 1: ASP7657 Single Ascending Dose

Experimental group

Treatment:

Drug: ASP7657

Part 1: ASP7657 Single Ascending Dose - Food Effect

Experimental group

Treatment:

Drug: ASP7657

Part 1: Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Part 2: ASP7657 Multiple Ascending Dose

Experimental group

Treatment:

Drug: ASP7657

Part 2: ASP7657 Multiple Ascending Dose Elderly

Experimental group

Treatment:

Drug: ASP7657

Part 2: Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Part 2: Naproxen

Active Comparator group

Treatment:

Drug: naproxen