Multiple Dose Study of DS-1971a

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: DS-1971a; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Hammersmith Medicines Research Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: July 11, 2014
• First Submitted That Met QC Criteria: July 11, 2014
• First Posted (Estimate): July 15, 2014

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; DS-1971a
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; DS-1971a
• Other Study ID Numbers: DS1971-A-E102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR