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Pharmacokinetics of ASP7657Phase 1NCT02108548

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

A Phase 1 study testing ASP7657 and naproxen in people with Pharmacokinetics of ASP7657 and Pharmacodynamics of ASP7657, run by Astellas Pharma Europe B.V. at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
ASP7657 and naproxen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
89 participants
Where
1 siteUnited Kingdom
Study dates
Apr 2014to Mar 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 22Show fewer
  • 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 locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Parexel Early Phase Clinical Unit

    Harrow, Middlesex, HA1 3UJ

Other trials in United Kingdom

About this study

Official title: 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

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

Read the 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).

Being tested
ASP7657, Placebo, naproxen
Keywords
ASP7657, Pharmacokinetics, Pharmacodynamics, Healthy Subjects, First in man, Safety

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ASP7657Drug

    oral

  • PlaceboDrug

    oral

  • naproxenDrug

    oral

Study groups in NCT02108548
Study groupRoleWhat they receive
Part 1: ASP7657 Single Ascending DoseExperimentalNot described
Receives: Drug: ASP7657
Part 1: ASP7657 Single Ascending Dose - Food EffectExperimentalNot described
Receives: Drug: ASP7657
Part 1: PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo
Part 2: ASP7657 Multiple Ascending DoseExperimentalNot described
Receives: Drug: ASP7657
Part 2: ASP7657 Multiple Ascending Dose ElderlyExperimentalNot described
Receives: Drug: ASP7657
Part 2: PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo
Part 2: NaproxenActive comparatorNot described
Receives: Drug: naproxen

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: Up to Day 20

Secondary outcomes (10)

  1. 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

    Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf), AUC from the time of dosing to the last measurable concentration (AUClast), time prior to the time corresponding to the first measurable (nonzero) concentration (tlag), time of maximum plasma concentration (tmax), maximum plasma concentration (Cmax), terminal elimination half-life (t ½), apparent volume of distribution during the terminal elimination phase after extravascular dosing (Vz/F), and apparent total systemic clearance after single or multiple extravascular dosing (CL/F)

    Measured: Day 1

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

    Cumulative amount of drug excreted in urine from time of dosing up to the collection time of the last measurable concentration (Aelast), cumulative amount of drug excreted in urine from time of dosing extrapolated to time infinity (Aeinf), percent of drug dose excreted in urine from time of dosing up to the collection time of the last measurable concentration (Aelast%), percent of drug dose excreted in urine from time of dosing extrapolated to time infinity (Aeinf%), renal clearance (CLr)

    Measured: Day 1

  3. 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)

    Measured: Day 1

  4. Part 1: PD in urine: Total urine volume over 24 hours

    Measured: Day -1 and Day 1

  5. 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)

    Measured: Day 1

  6. Part 2: PK of ASP7657 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)

    Measured: Days 2, 4, 6, 8, 10 and 12

  7. 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)

    Measured: Day 14

  8. PK profile of ASP7657 after last dose in urine: Aetau, (Aetau%), and CLr

    Cumulative amount of drug excreted in urine from the time of dosing to the start of the next dosing interval (Aetau), percent of drug dose excreted in urine over the time interval between consecutive dosing (Aetau%)

    Measured: Day 14

  9. Part 2: PD profile of plasma renin activity and aldosterone

    Measured: Days -1, 7, and 14

  10. Part 2: PD of urine electrolytes: amount excreted over 24 hours (Ae24)

    Measured: Days -1 and 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2014 (estimated)
  2. Study startApr 2014
  3. Primary completionMar 2015
  4. Study completionMar 2015

Why it stopped: Gastrointestinal safety findings

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Factorial
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02108548
Sponsor's protocol ID
7657-CL-0001
Other IDs
2013-004357-25
Status last verified
Mar 2015
First submitted
7 Apr 2014
Last updated
27 Mar 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ASP7657 and naproxen in people with Pharmacokinetics of ASP7657 and Pharmacodynamics of ASP7657, run by Astellas Pharma Europe B.V. at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Gastrointestinal safety findings). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02108548.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2015.

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