Study to Evaluate the Safety and Pharmacokinetics of Single Doses of ASP2151 in Healthy Male Subjects and the Effects of Food

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and tolerability of single rising doses of ASP2151 under fasted condition in healthy male subjects. The study will also evaluate the pharmacokinetics (PK) of a single dose of ASP2151 under fasted versus fed conditions in healthy male subjects.

Detailed Description
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Study will be divided into two parts. Part 1 will evaluate the safety and tolerability of ASP2151 single rising doses in groups A-H in fasted condition and to determine the maximum tolerable dose (MTD) if possible. Part 2 will evaluate the effect of fasted versus fed conditions on the safety, tolerability and PK of a single dose of ASP2151 in two treatment cycles. The wash-out period between the two treatment cycles will be at least 5 days and not shorter than five times the average elimination half-life of ASP2151, as determined in part 1 of the study.

Official Title
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A Double-Blind, Placebo-Controlled Single Dose Escalating Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP2151 in Healthy Male Subjects, Followed by an Open, Two-Period Crossover Study to Assess the Effect of Fed Conditions on the Safety, Tolerability and Pharmacokinetics of ASP2151

Conditions
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Herpes Genitalis, Herpes Zoster

Intervention / Treatment
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* Drug: ASP2151
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight between 60 and 100 kg, and BMI between 18 and 30 kg/m2 inclusive Exclusion Criteria: Known or suspected hypersensitivity to ASP2151 or any components of the formulation used Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug Any clinically significant history of genital herpes symptoms and/or herpes zoster symptoms in the 3 months prior to admission to the Clinical Unit Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic Abnormal pulse rate and/or blood pressure measurements at the pre-study visit as follows: Pulse rate <40 or >90 bpm (beats per minute); mean systolic blood pressure <90 or >140 mmHg (millimeter of mercury); mean diastolic blood pressure <40 or >95 mmHg Regular use of any prescribed or OTC (over the counter) drugs in the 4 weeks prior to admission to the Clinical Unit OR any use of such drugs in the 2 weeks prior to admission to the Clinical Unit Any use of drugs of abuse within 3 months prior to admission to the Clinical Unit History of smoking more than 10 cigarettes per day within 3 months prior to admission to the Clinical Unit History of drinking more than 21 units of alcohol per week within 3 months prior to admission to the Clinical Unit Donation of blood or blood products within 3 months, prior to admission to the Clinical Unit Positive serology test for HBsAg (Hepatitis B surface antigen), HAV IgM (Hepatitis A Virus), anti-HCV (Hepatitis C Virus) or anti-HIV (Human Immunodeficiency Virus) 1 and 2 Not willing or able to swallow size 00 capsules

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: ASP2151 Single Ascending Dose Group A (Fasting)<br>Participants will receive single dose of ASP2151 assigned to Group A on day 1 | Drug: ASP2151<br>* Oral<br>|
| Experimental: Part 1: ASP2151 Single Ascending Dose Group B (Fasting)<br>Participants will receive single dose of ASP2151 assigned to Group B on day 1 | Drug: ASP2151<br>* Oral<br>|
| Experimental: Part 1: ASP2151 Single Ascending Dose Group C (Fasting)<br>Participants will receive single dose of ASP2151 assigned to Group C on day 1 | Drug: ASP2151<br>* Oral<br>|
| Experimental: Part 1: ASP2151 Single Ascending Dose Group D (Fasting)<br>Participants will receive single dose of ASP2151 assigned to Group D on day 1 | Drug: ASP2151<br>* Oral<br>|
| Experimental: Part 1: ASP2151 Single Ascending Dose Group E (Fasting)<br>Participants will receive single dose of ASP2151 assigned to Group E on day 1 | Drug: ASP2151<br>* Oral<br>|
| Experimental: Part 1: ASP2151 Single Ascending Dose Group F (Fasting)<br>Participants will receive single dose of ASP2151 assigned to Group F on day 1 | Drug: ASP2151<br>* Oral<br>|
| Placebo Comparator: Part 1: Placebo Single Ascending Dose (Fasting)<br>Participants will receive single dose of matching placebo on day 1 | Drug: Placebo<br>* Oral<br>|
| Experimental: Part 2: ASP2151 (Fasting)<br>Participants will receive a single dose of ASP2151 under fasted conditions on day 1 in the first treatment period (period 1). Following a wash-out period of at least five days, the treatment will be repeated in the reverse orientation (period 2) | Drug: ASP2151<br>* Oral<br>|
| Experimental: Part 2: ASP2151 (Fed)<br>Participants will receive a single dose of ASP2151 under fed conditions on day 1 in the first treatment period (period 1). Following a wash-out period of at least five days, the treatment will be repeated in the reverse orientation (period 2) | Drug: ASP2151<br>* Oral<br>|
| Experimental: Part 1: ASP2151 Single Ascending Dose Group G (Fasting)<br>Participants will receive single dose of ASP2151 assigned to Group G on day 1 | Drug: ASP2151<br>* Oral<br>|
| Experimental: Part 1: ASP2151 Single Ascending Dose Group H (Fasting)<br>Participants will receive single dose of ASP2151 assigned to Group H on day 1 | Drug: ASP2151<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability assessed by nature, frequency, and severity of Adverse Events (AEs) | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by 12- lead electrocardiogram (ECG) | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by vital sign measurement: blood pressure | For Part 1 and Part 2 includes systolic and blood diastolic pressure | Up to Day 15 of each treatment period | 
| Safety assessed by vital sign measurement: pulse rate | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by laboratory test: biochemical | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by laboratory test: hematological | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by laboratory test: serology | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by laboratory test: urinalysis | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by physical exam: body weight | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by physical exam: height | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 
| Safety assessed by physical exam: body mass index (BMI) | For Part 1 and Part 2 | Up to Day 15 of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of ASP2151 in plasma: AUC0-inf | For Part 1 and 2. AUC0-inf: Area under the concentration time curve from the time of dosing extrapolated to time infinity | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in plasma: t1/2 | For Part 1 and 2. t1/2: Apparent terminal elimination half-life | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in plasma: Cmax | For Part 1 and 2. Cmax: Maximum concentration | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in plasma: tmax | For Part 1 and 2. tmax: The time after dosing when Cmax occurs | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in plasma: CL/F | For Part 1 and 2. CL/F: Oral clearance | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in plasma: Vz/F | For Part 1 and 2. Vz/F: Apparent volume of distribution | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in plasma: AUClast | For Part 1 and 2. AUClast: Area under the plasma concentration time curve from time of dosing up to the last quantifiable sample | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in plasma: tlag | For Part 1 and 2. tlag: Absorption lag time | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in urine: Aelast | For Part 1 and 2. Aelast: Amount excreted unchanged in urine from time of dosing up to the last quantifiable sample | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in urine: Ae0-inf | For Part 1 and 2. Ae0-inf: Amount excreted unchanged in urine from time of dosing extrapolated to infinity | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in urine: Ae% | For Part 1 and 2. Ae%: Percent of ASP2151 amount excreted in urine | Up to 48 hours in each treatment period | 
| Pharmacokinetics of ASP2151 in urine: CLr | For Part 1 and 2. CLr: Renal clearance | Up to 48 hours in each treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety of ASP2151, Phase 1, Pharmacokinetics, Healthy male subjects, Tolerability, Food effect of ASP2151