A Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP3700 in Healthy Male Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics of ASP3700
• Intervention / Treatment: Drug: Placebo; Drug: ASP3700; Drug: itraconazole

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • PAREXEL Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP3700 single ascending dose cohort; Part 1	Drug: ASP3700; oral
Placebo Comparator: Placebo single ascending dose cohort; Part 1	Drug: Placebo; oral
Experimental: ASP3700 alone; Part 2	Drug: ASP3700; oral
Active Comparator: ASP3700 and itraconazole; Part 2	Drug: ASP3700; oral; Drug: itraconazole; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by adverse events (Part 1)		up to end of study visit (up to 16 days)
Safety as assessed by vital signs (Part 1)		up to end of study visit (up to 16 days)
Safety as assessed by laboratory tests (Part 1)	Laboratory tests includes the measurement of sex-hormone related biomarkers and exploratory renal biomarkers.	up to end of study visit (up to 16 days)
Safety as assessed by electrocardiogram (ECG) measurements (Part 1)	ECG measurements include routine 12-lead ECG, continuous cardiac monitoring (Holter ECG) and real-time cardiac monitoring (ECG telemetry)	up to end of study visit (up to 16 days)
Safety as assessed by Bond and Lader VAS (Part 1)	visual analogue scale (VAS)	Up to Day 2
Safety as assessed by C-SSRS (Part 1)	Columbia - Suicide Severity Rating Scale (C-SSRS)	Up to end of study visit (up to 16 days)
Safety as assessed by ARCI-49 (Part 1)	Addiction Research Center Inventory (ARCI)-49 (49-item)	Up to Day 2
Pharmacokinetic parameter of itraconazole (plasma): Ctrough (Part 2)	Concentration immediately prior to dosing at multiple dosing	Days 3-13
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUCinf (Part 2)	Area under the concentration-time curve from time of dosing extrapolated to time infinity (AUCinf)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUCinf (%extrap) (Part 2)	Percentage of AUCinf due to extrapolation from tlast to time infinity (AUCinf [%extrap])	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUClast (Part 2)	Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): Cmax (Part 2)	Maximum concentration (Cmax)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma):λz (Part 2)	Terminal elimination rate constant (λz)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): MRT (Part 2)	Mean residence time (MRT)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): tlag (Part 2)	Time prior to the time corresponding to the first measurable (nonzero) concentration (tlag)	Day 1 (period 1 and 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): tmax (Part 2)	Time of maximum concentration (tmax)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): t1/2 (Part 2)	Terminal elimination half-life (t1/2)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): Vz/F (Part 2)	Apparent volume of distribution during the terminal elimination phase after extravascular dosing (Vz/F)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aelast (Part 2)	Cumulative amount of study drug excreted into urine from time of dosing up to the collection time of the last measurable concentration (Aelast)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aeinf (Part 2)	Cumulative amount of study drug excreted into urine from time of dosing extrapolated to time infinity (Aeinf)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aelast% (Part 2)	Percentage of study drug excreted into urine from the time of dosing up to the collection time of the last measurable concentration (Aelast%)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aeinf% (Part 2)	Percentage of study drug excreted into urine from time of dosing extrapolated to time infinity (Aeinf%)	Days 1-7 (period 1) and Days 1-13 (period 2)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): CLR (Part 2)	Renal clearance (CLR)	Days 1-7 (period 1) and Days 1-13 (period 2)
Safety as assessed by orthostatic evaluation (or blood pressure change in orthostatic challenge test) (Part 1)		Up to Day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite of pharmacokinetics of ASP3700: AUCinf, AUCinf(%extrap), AUClast, Cmax, CL/F, λz, MRT, tlag, tmax, t½, Vz/F (plasma) (Part 1)	up to Day 7
Title: Composite of pharmacokinetics of ASP3700: Aelast, Aeinf, Aelast%, Aeinf%, CLR (urine) (Part 1)	up to Day 7
Safety as assessed by adverse events, vital signs, orthostatic evaluation, laboratory tests, ECG measurements, C-SSRS, Bond & Lader VAS, ARCI-49 (Part 2)	Days 1-7 (period 1) and Days 1-13 (period 2) and at end of study visit (up to 22 days)

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 4, 2014

Study Record Updates

• Last Update Posted (Estimate): October 30, 2014
• Last Update Submitted That Met QC Criteria: October 29, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Healthy volunteers; Pharmacokinetics; Itraconazole; Drug-drug interaction; ASP3700
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 3700-CL-0001; 2013-005018-36 (EudraCT Number)