Clinical Trials/NCT02108548

NCT02108548

Terminated

Phase 1

A Phase 1 Ascending Single and Multiple Oral Dose Study to Assess the Safety and Tolerability, Including Gastrointestinal Safety, Pharmacokinetics and Pharmacodynamics of ASP7657 in Caucasian Healthy Male and Female Subjects, Including a Food Effect Cohort

Astellas Pharma Europe B.V.1 site in 1 country89 target enrollmentApril 2014

ConditionsPharmacokinetics of ASP7657 Pharmacodynamics of ASP7657 Healthy Subjects

InterventionsASP7657 naproxen Placebo

DrugsASP7657 Placebo naproxen

Overview

Phase: Phase 1
Intervention: ASP7657
Conditions: Pharmacokinetics of ASP7657
Sponsor: Astellas Pharma Europe B.V.
Enrollment: 89
Locations: 1
Primary Endpoint: 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)
Status: Terminated
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed 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).

Registry

clinicaltrials.gov

Start Date

April 2014

End Date

March 2015

Last Updated

11 years ago

Study Type

Interventional

Study Design

Factorial

Sex

All

Investigators

Sponsor

Astellas Pharma Europe B.V.

Responsible Party

Sponsor

Eligibility Criteria

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 -
•(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)

Arms & Interventions

Part 1: ASP7657 Single Ascending Dose - Food Effect

Intervention: ASP7657

Part 2: Naproxen

Intervention: naproxen

Part 1: ASP7657 Single Ascending Dose

Intervention: ASP7657

Part 1: Placebo

Intervention: Placebo

Part 2: ASP7657 Multiple Ascending Dose

Intervention: ASP7657

Part 2: ASP7657 Multiple Ascending Dose Elderly

Intervention: ASP7657

Part 2: Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

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)

Time Frame: Up to Day 20

Secondary Outcomes

Part 2: PD profile of plasma renin activity and aldosterone(Days -1, 7, and 14)
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)
Part 2: PD of urine electrolytes: amount excreted over 24 hours (Ae24)(Days -1 and 14)
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 last dose in plasma: AUC from the time of dosing to the start of the next dosing interval (AUCtau), tmax, Cmax, t ½, Vz/F, CL/F, Accumulation ration (Racc), peak-trough ratio (PTR)(Day 14)
PK profile of ASP7657 after last dose in urine: Aetau, (Aetau%), and CLr(Day 14)
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 2: PK of ASP7657 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)(Days 2, 4, 6, 8, 10 and 12)