Clinical trial NCT02155504: A Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP3700 in Healthy Male Subjects
Official title: A Phase 1, Single Ascending Oral Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP3700 in Healthy Male Subjects, Including a Drug-drug Interaction Part With Itraconazole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Pharmacokinetics of ASP3700
Keywords: Healthy volunteers
Pharmacokinetics
ASP3700
Itraconazole
Drug-drug interaction
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-06-04
Enrollment: 44
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: 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, tolerability and pharmacokinetics (PK) of single ascending oral doses of ASP3700 in healthy male subjects. This study will also explore the effect of itraconazole (another drug) on the PK of ASP3700, as well as to evaluate the safety and tolerability of ASP3700 alone and in combination with itraconazole in healthy male subjects.

Detailed description: This study consists of 2 parts: Part 1 is a single ascending dose study where subjects will receive either ASP3700 or matching placebo; Part 2 is a drug-drug interaction (DDI) open-label, crossover study comprised of 1 sequence with 2 investigational periods where subjects will receive ASP3700 alone and in combination with itraconazole.

Eligibility criteria: Inclusion Criteria:

* Subject has a body mass index range of 18.5 - 30.0 kg/m2. The subject weighs at least 50 kg.
* Subject and his female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continue throughout the clinical study period and for 90 days after the final study drug administration.
* Subject must not donate sperm starting at screening and throughout the clinical study period and for 90 days after the final study drug administration.

Exclusion Criteria:

* Subject has a known or suspected hypersensitivity to ASP3700 (parts 1 and 2) or itraconazole (part 2 only) or significant adverse reactions to historical cannabinoid use or any components of the formulations used.
* Subject has any of the liver function tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase, gamma-glutamyl transaminase, total bilirubin \[TBL\]) above the upper limit of normal (ULN). In such a case the assessment may be repeated once (upon admission to the clinical unit).
* Subject has a history of a suicide attempt or suicidal behavior. Any recent suicidal ideation within the last 3 months or who are at significant risk to commit suicide, as judged by the Investigator using the C-SSRS (a level of 4 or 5) at screening or upon admission to the clinical unit.
* Subject has any clinically significant abnormality following the Investigator's review of the physical examination, ECG and clinical study protocol-defined clinical laboratory tests at screening or upon admission to the clinical unit.
* Subject has a pulse rate \< 40 or \> 90 beats per minute; mean SBP \> 140 mmHg; mean DBP \> 90 mmHg (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse rate will be measured automatically) upon admission to the clinical unit.
* Subject has a mean corrected QT interval using Fridericia's formula (QTcF) interval \> 430 ms at day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken.
* 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 more than 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 \[12%\]) within 3 months prior to admission to the clinical unit.
* Subject has consumed grapefruit, grapefruit-containing products or Seville orange-containing products within 72 hours prior to admission to the clinical unit.

Primary outcomes:
measure: Safety as assessed by adverse events (Part 1)
timeFrame: up to end of study visit (up to 16 days)
measure: Safety as assessed by vital signs (Part 1)
timeFrame: up to end of study visit (up to 16 days)
measure: Safety as assessed by laboratory tests (Part 1)
timeFrame: up to end of study visit (up to 16 days)
measure: Safety as assessed by electrocardiogram (ECG) measurements (Part 1)
timeFrame: up to end of study visit (up to 16 days)
measure: Safety as assessed by Bond and Lader VAS (Part 1)
timeFrame: Up to Day 2
measure: Safety as assessed by C-SSRS (Part 1)
timeFrame: Up to end of study visit (up to 16 days)
measure: Safety as assessed by ARCI-49 (Part 1)
timeFrame: Up to Day 2
measure: Pharmacokinetic parameter of itraconazole (plasma): Ctrough (Part 2)
timeFrame: Days 3-13
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUCinf (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUCinf (%extrap) (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUClast (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): Cmax (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma):λz (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): MRT (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): tlag (Part 2)
timeFrame: Day 1 (period 1 and 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): tmax (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): t1/2 (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): Vz/F (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aelast (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aeinf (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aelast% (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aeinf% (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): CLR (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2)
measure: Safety as assessed by orthostatic evaluation (or blood pressure change in orthostatic challenge test) (Part 1)
timeFrame: Up to Day 7
Secondary outcomes:
measure: Composite of pharmacokinetics of ASP3700: AUCinf, AUCinf(%extrap), AUClast, Cmax, CL/F, λz, MRT, tlag, tmax, t½, Vz/F (plasma) (Part 1)
timeFrame: up to Day 7
measure: Title: Composite of pharmacokinetics of ASP3700: Aelast, Aeinf, Aelast%, Aeinf%, CLR (urine) (Part 1)
timeFrame: up to Day 7
measure: Safety as assessed by adverse events, vital signs, orthostatic evaluation, laboratory tests, ECG measurements, C-SSRS, Bond & Lader VAS, ARCI-49 (Part 2)
timeFrame: Days 1-7 (period 1) and Days 1-13 (period 2) and at end of study visit (up to 22 days)
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Parexel Early Phase Clinical Unit
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Medical Director
role: STUDY_DIRECTOR
References: