Clinical trial NCT02314793: A Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP2205 in Healthy Young Males and Females and Elderly Females and to Evaluate the Effect of Food on the Pharmacokinetics of a Single Dose of of ASP2205
Official title: A Phase 1 Single and Multiple Ascending Oral Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP2205 in Healthy Young Males and Females and Elderly Females and to Evaluate the Effect of Food on the Pharmacokinetics of a Single Dose of ASP2205
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Subjects
Pharmacokinetics of ASP2205
Keywords: Pharmacokinetics
ASP2205
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-12-11
Enrollment: 93
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the safety and tolerability of single ascending oral doses of ASP2205 in healthy young male and female subjects. This study will also evaluate the safety and tolerability of multiple ascending oral doses of ASP2205 in healthy young and elderly female subjects.

Detailed description: Part 1 is a single ascending dose investigator-blinded study in healthy young male and female subjects. Six doses of ASP2205 or matching placebo will be given to separate cohorts consisting of 8 subjects each, with 6 subjects receiving ASP2205 and 2 subjects receiving matching placebo. ASP2205 or matching placebo will be given as a single oral dose under fasted conditions.

The effect of a high-calorie high-fat meal (breakfast) on the safety, tolerability and pharmacokinetics of a single oral dose of ASP2205 will be evaluated in a separate cohort of 8 subjects in an open-label manner.

Part 2 is a multiple ascending dose subject- and investigator-blinded study comprising 3 cohorts with each 12 healthy young (aged 25 to 55 years) female subjects and 1 cohort with 12 healthy elderly (aged 65 years or older) female subjects who will receive ASP2205 or matching placebo. Nine subjects in each cohort will be treated with ASP2205 and 3 subjects will be treated with matching placebo (ratio 3:1).

Eligibility criteria: Inclusion Criteria:

* Subject is a healthy young male or female subject aged 25 to 55 years, inclusive, at screening (part 1 and 2) or healthy elderly female subject aged ≥ 65 years, inclusive, at screening (part 2 only).
* Subject has a body mass index (BMI) range of 18.5 - 30.0 kg/m2, inclusive. The subject weighs at least 50 kg (at screening).
* Subject agrees not to participate in another interventional study while participating in the present study, defined as signing the informed consent form until completion of the last study visit.

Exclusion Criteria:

* Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
* Subject has a known or suspected hypersensitivity to ASP2205 or any components of the formulations used.
* Subject has any of the liver function tests (LTs; aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase (ALP), gamma glutamyl transferase, total bilirubin \[TBL\]) above the upper limit of normal (ULN). In such a case, the assessment may be repeated once (admission to the clinical unit).
* Subject has at screening any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies).
* Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic (including surgical procedures to treat pelvic trauma), 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 admission to the clinical unit.
* Subject has a relevant history of attempted suicide or suicidal behavior. Any recent suicidal ideation within the last 6 months or who are at significant risk to commit suicide.
* Subject has any clinically significant abnormality.
* Subject has a mean pulse \< 40 or \> 90 bpm; mean systolic blood pressure (SBP) \> 140 mmHg; mean DBP \> 90 mmHg (elderly subjects: mean SBP \> 160 mmHg; mean DBP \> 100 mmHg) (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) prior to the admission to the clinical unit (triplicates taken at screening and on admission to the clinical unit). If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken.
* Subject has a mean corrected QT interval using Fridericia's formula (QTcF) \> 430 ms (for male subjects) and \> 450 ms (for female subjects) at admission to the clinical unit. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken.
* Subject uses any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to study drug administration, except for occasional use of paracetamol (up to 2 g/day) and except for use of contraceptives or hormone replacement therapy.
* Subject has a history of smoking within 6 months prior to admission to the clinical unit.
* Subject has a history of drinking \> 21 units 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 \[12%\]) (\> 14 units of alcohol for female subjects) within 3 months prior to admission to the clinical unit.
* Subject uses grapefruit juice (more than 3 × 200 mL) or products containing grapefruit and/or Seville oranges (more than 3 times) in the week prior to admission to the clinical unit until ESV, as reported by the subject.
* Subject uses any drugs of abuse within 3 months prior to admission to the clinical unit.
* Subject regularly uses any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to admission to the clinical unit.
* Subject had significant blood loss, donated 1 unit (500 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 admission to the clinical unit.
* Subject has a positive serology test for hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (immunoglobulin M) (anti-HAV \[IgM\]), hepatitis C virus antibodies (anti-HCV) or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) at screening.
* Subject has been treated with any investigational drugs within 90 days or 5 terminal half-lives, whichever is longer, prior to drug administration.
* Subject is unable to communicate, read and understand English, or has any other condition which makes the subject unsuitable for study participation.
* Subject is an employee of the Astellas Group or Clinical Research Organization involved in the study.

Primary outcomes:
measure: Part 1 and Part 2: Safety assessed by nature, frequency and severity of adverse events
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety assessed by vital signs
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety assessed by orthostatic challenge test
timeFrame: up to 29 days
measure: Part 1 and Part 2: Assessment of clinical laboratory tests
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety assessed by routine 12 lead electrocardiogram (ECG)
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety assessed by continuous cardiac monitoring (Holter ECG)
timeFrame: up to 29 days
measure: Part 1: Safety assessed by real-time cardiac monitoring (ECG telemetry)
timeFrame: up to 16 days
Secondary outcomes:
measure: Part 1 and Part 2: Safety laboratory test: prolactin
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety laboratory test: cortisol
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety laboratory test: bicarbonate (HCO3)
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety assessed by chemistry profile
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety laboratory test: fasting blood glucose
timeFrame: up to 29 days
measure: Part 1 and Part 2: Safety laboratory test: creatinine urine
timeFrame: up to 29 days
measure: Part 1: Central nervous system (CNS) safety monitoring: Bond & Lader visual analogue scale (VAS)
timeFrame: up to 4 days
measure: Part 1: CNS safety monitoring: Drug effects questionnaire (DEQ) VAS
timeFrame: up to 4 days
measure: Part 1: Pharmacokinetics profile of ASP2205 in plasma: AUCinf, AUCinf (% extrapolated), AUClast, AUC24, CL/F, Cmax, terminal elimination rate constant, MRT, tlag, tmax, t1/2, Vz/F
timeFrame: Day 1
measure: Part 1: Pharmacokinetics profile of ASP2205 in urine: Aeinf, Aeinf%, Aelast, Aelast%, CLR
timeFrame: Day 1
measure: Part 2: Safety laboratory test: di-docosahexaenoyl-bis(monoacylglycerol) phosphate (di-22:6-BMP) in serum and urine
timeFrame: up to 29 days
measure: Part 2: CNS safety monitoring: CogState's neurocognition test battery (short version)
timeFrame: up to 14 days
measure: Part 2: CNS safety monitoring: Bond & Lader VAS
timeFrame: up to 17 days
measure: Part 2: CNS safety monitoring: DEQ VAS
timeFrame: Time Frame : up to 13 days
measure: Part 2: CNS safety monitoring: Addiction Research Center Inventory (49-item short form) (ARCI-49)
timeFrame: up to 13 days
measure: Part 2: CNS safety monitoring: Physician Withdrawal Checklist
timeFrame: up to 29 days
measure: Part 2: CNS safety monitoring: Columbia - Suicide Severity Rate Scale (C-SSRS)
timeFrame: up to 29 days
measure: Part 2: Appetite visual analogue scale (AVAS)
timeFrame: up to 15 days
measure: Part 2: Nausea VAS
timeFrame: up to 15 days
measure: Part 2: Body weight
timeFrame: up to 29 days
measure: Part 2: Total daily urine production (24-hour volume)
timeFrame: up to 15 days
measure: Part 2: Total daily urine osmolality (24 hour pooled sample from each void)
timeFrame: up to 15 days
measure: Part 2: Total daily fluid intake
timeFrame: up to 15 days
measure: Part 2: Pharmacokinetic profile of ASP2205 in plasma: AUC24, Cmax, tlag, tmax
timeFrame: Day 1
measure: Part 2: Pharmacokinetic parameter: Ctrough
timeFrame: Day 1 immediately prior to dosing (morning Ctrough and, only in case of twice daily dosing, evening C trough): days 2, 4, 6, 8, 10, 12
measure: Part 2: Pharmacokinetic profile of ASP2205 in plasma: AUCtau, Cmax, tmax
timeFrame: Days 12, 13 (in case of twice daily dosing)
measure: Part 2: Pharmacokinetic profile of ASP2205 in plasma: AUCtau, CL/F, Cmax, terminal elimination rate constant, MRT, peak trough ratio (PTR), accumulation ratio calculated using the area under the concentration -time curve [Rac(AUC)], tmax, t1/2, VzF
timeFrame: Day 14
measure: Part 2: Pharmacokinetic profile of ASP2205 in urine: Aetau, Aetau%, CLR
timeFrame: Day 14
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Site GB44001
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Associate Medical Director
role: STUDY_DIRECTOR
References: