Multiple Dose Study of DS-1971a

Study Overview
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Brief Summary
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This is a randomised, double-blind, placebo-controlled multiple dose study designed to explore the safety, tolerability and PK of DS-1971a following oral administration over 14 days to healthy male subjects.

Official Title
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A PHASE I, DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED, MULTIPLE-DOSE STUDY TO ASSESS SAFETY, TOLERABILITY AND PHARMACOKINETICS OF DS-1971A IN HEALTHY MALE SUBJECTS

Conditions
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Healthy

Intervention / Treatment
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* Drug: DS-1971a
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged 18-55 years. A body mass index (BMI) in the range 18-30 kg/m2, inclusive, and weighing between 50 and 100 kg at screening. Willing to comply with all study restrictions, including the use of contraception, concomitant medication, and dietary and lifestyle restrictions. Sufficient intelligence to understand the nature of the study and any hazards of participating in it. Ability to communicate satisfactorily with the Investigator and to participate in, and comply with requirements of, the entire study. Have given written consent to participate in the study after reading the ICF, and after having the opportunity to discuss the study with the Investigator or his delegate. Have given written consent to have his data entered into The Over-volunteering Prevention System. Exclusion Criteria: Clinically relevant abnormal history, physical findings, ECG findings, or laboratory values that could interfere with the objectives of the study or compromise the safety of the subject. Presence or history of acute or chronic illness, including (but not limited to) liver or kidney disease, hypertension, seizures, or any known impairment of endocrine, or other specific body-organ dysfunction. History of serious reaction to any medicine. Presence or history of malignant disease. Acute or chronic infectious disease, including human immunodeficiency virus (HIV), hepatitis B virus (HBV) or C virus (HCV) infection. Surgery (eg stomach bypass) or medical condition that might affect how the body handles or absorbs medicines. Significant illness within 4 weeks before the first dose of study medication. Participation in another clinical study of a new chemical entity or a prescription medicine within the previous 3 months, or unwilling to abstain from participating in other clinical trials during the study and for 3 months after receipt of study medication. Participation in another clinical study with DS 1971a. Abnormal ECG waveform morphology at screening that would preclude accurate measurement of the QT interval duration. Corrected QT interval (Fridericia's formula) (QTcF) interval duration > 430 msec, obtained as an average from the measurements on duplicate screening ECGs. Estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73m2 (based on Modification of Diet in Renal Disease [MDRD] equation) or an absolute creatinine value outside the normal range. Use of any prescription or over the counter (OTC) medications, or herbal remedies (such as St John's wort), known to be strong inhibitors or strong inducers of cytochrome (CYP) enzymes (also known as CYP P450 enzymes) during the 30 days before the first dose of study medication; use of any other prescription or OTC medicine (with the exception of acetaminophen (paracetamol)), including dietary supplements or herbal remedies, during the 7 days before the dose of study medication. Consumption of certain foods or beverages before the first dose and throughout the study period. Loss of more than 400 mL blood or donation of blood, plasma, platelets, or any other blood components during the 3 months before the first dose of study medication, or unwilling to abstain from doing so during the study and for 3 months after receipt of study medication. Abuse of drugs or alcohol during the 2 years before the first dose of study medication, or intake of more than 21 units of alcohol weekly. Use of tobacco products or nicotine-containing products during the 3 months before the first dose of study medication and during the study. Evidence of drug or alcohol abuse at screening or admission. Likely possibility that the volunteer will not cooperate with the requirements of the protocol. Objection by GP to the volunteer entering the study.

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DS-1971a<br>DS-1971a suspension, up to 4650mg/day | Drug: DS-1971a<br>* suspension<br>|
| Placebo Comparator: placebo<br>matching DS-1971a suspension | Drug: placebo<br>* placebo matching DS-1971a<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | To assess the safety and tolerability of repeated oral doses of DS-1971a in healthy male subjects the number, severity, and frequency of adverse events will be recorded from enrollment through discharge from study, up to 2 months. | up to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| characterise the plasma pharmacokinetics AUC (area under curve) | To characterise the plasma pharmacokinetics (PK) of DS-1971a in healthy male subjects receiving repeated oral doses. plasma concentrations of DS 1971a, and derived PK parameters: AUC (area under curve); Cmax (maximum concentration); Tmax (time of maximum concentration), T½ (terminal half-life), CL/F; Vss/F | Day 1 through Day 17 | 
| characterise the plasma pharmacokinetics Cmax (maximum concentration) | To characterise the plasma pharmacokinetics (PK) of DS-1971a in healthy male subjects receiving repeated oral doses. plasma concentrations of DS 1971a, and derived PK parameters: AUC (area under curve); Cmax (maximum concentration); Tmax (time of maximum concentration), T½ (terminal half-life), CL/F; Vss/F | Day 1 through Day 17 | 
| characterise the plasma pharmacokinetics Tmax (time of maximum concentration) | To characterise the plasma pharmacokinetics (PK) of DS-1971a in healthy male subjects receiving repeated oral doses. plasma concentrations of DS 1971a, and derived PK parameters: AUC (area under curve); Cmax (maximum concentration); Tmax (time of maximum concentration), T½ (terminal half-life), CL/F; Vss/F | Day 1 through Day 17 | 
| characterise the plasma pharmacokinetics T½ (terminal half-life) | To characterise the plasma pharmacokinetics (PK) of DS-1971a in healthy male subjects receiving repeated oral doses. plasma concentrations of DS 1971a, and derived PK parameters: AUC (area under curve); Cmax (maximum concentration); Tmax (time of maximum concentration), T½ (terminal half-life), CL/F; Vss/F | Day 1 through Day 17 | 
| characterise the plasma pharmacokinetics CL/F (apparent oral clearance) | To characterise the plasma pharmacokinetics (PK) of DS-1971a in healthy male subjects receiving repeated oral doses. plasma concentrations of DS 1971a, and derived PK parameters: AUC (area under curve); Cmax (maximum concentration); Tmax (time of maximum concentration), T½ (terminal half-life), CL/F (apparent oral clearance); Vss/F | Day 1 through Day 17 | 
| characterise the plasma pharmacokinetics Vss/F (apparent volume of distribution) | To characterise the plasma pharmacokinetics (PK) of DS-1971a in healthy male subjects receiving repeated oral doses. plasma concentrations of DS 1971a, and derived PK parameters: AUC (area under curve); Cmax (maximum concentration); Tmax (time of maximum concentration), T½ (terminal half-life), CL/F (apparent oral clearance); Vss/F (apparent volume of distribution). | Day 1 through Day 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, pharmacokinetics, DS-1971a